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class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/109504767/Wavelet_Transform_Based_De_Noising_for_Two_Photon_Imaging_of_Synaptic_Ca_2_Transients"><img alt="Research paper thumbnail of Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients" class="work-thumbnail" src="https://attachments.academia-assets.com/108769205/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/109504767/Wavelet_Transform_Based_De_Noising_for_Two_Photon_Imaging_of_Synaptic_Ca_2_Transients">Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients</a></div><div class="wp-workCard_item"><span>Biophysical Journal</span><span>, Mar 1, 2013</span></div><div class="wp-workCard_item 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text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688180/A_stochastic_model_of_hippocampal_synaptic_plasticity_with_geometrical_readout_of_enzyme_dynamics">A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Discovering the rules of synaptic plasticity is an important step for understanding brain learnin...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing plasticity models are either 1) top-down and interpretable, but not flexible enough to account for experimental data, or 2) bottom-up and biologically realistic, but too intricate to interpret and hard to fit to data. We fill the gap between these approaches by uncovering a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to plasticity outcomes. We apply this readout to a multi-timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental condit...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1396cab7f16772f71892fe6191d17a0a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":86987972,"asset_id":80688180,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/86987972/download_file?st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688180"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688180"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688180; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80688180]").text(description); $(".js-view-count[data-work-id=80688180]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80688180; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80688180']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 80688180, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1396cab7f16772f71892fe6191d17a0a" } } $('.js-work-strip[data-work-id=80688180]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80688180,"title":"A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics","translated_title":"","metadata":{"abstract":"Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing plasticity models are either 1) top-down and interpretable, but not flexible enough to account for experimental data, or 2) bottom-up and biologically realistic, but too intricate to interpret and hard to fit to data. We fill the gap between these approaches by uncovering a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to plasticity outcomes. We apply this readout to a multi-timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental condit...","publisher":"Cold Spring Harbor Laboratory","publication_date":{"day":null,"month":null,"year":2021,"errors":{}}},"translated_abstract":"Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing plasticity models are either 1) top-down and interpretable, but not flexible enough to account for experimental data, or 2) bottom-up and biologically realistic, but too intricate to interpret and hard to fit to data. We fill the gap between these approaches by uncovering a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to plasticity outcomes. We apply this readout to a multi-timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental condit...","internal_url":"https://www.academia.edu/80688180/A_stochastic_model_of_hippocampal_synaptic_plasticity_with_geometrical_readout_of_enzyme_dynamics","translated_internal_url":"","created_at":"2022-06-04T09:42:09.945-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":86987972,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987972/thumbnails/1.jpg","file_name":"2021.03.30.437703.full.pdf","download_url":"https://www.academia.edu/attachments/86987972/download_file?st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"A_stochastic_model_of_hippocampal_synapt.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987972/2021.03.30.437703.full-libre.pdf?1654361892=\u0026response-content-disposition=attachment%3B+filename%3DA_stochastic_model_of_hippocampal_synapt.pdf\u0026Expires=1732417379\u0026Signature=hS6a6vZA6RrczqOlCmqbi2dTu2i0recqixmBHf0DhfcX~QQkX3qLW5O2-XOV8Jka5GWiIpzwjayHN0KDOqbA4bQ7knJcnJR4nfbmYFRY2wnYmMyncj7WP-dzk4sty2A4n3~D2nJVluQ8InER6Shk1Ig56azyPgeGHRsSumCOOFKYjCRZiN0zOWjXVyvlsRR24GFHwDEGAw9OLgoE2EGBDCAjLRwnb3VXtjrir~KtfePzxxaemk7GMMTgTTp9JBC5pd2LSGIJ65HG~FrXLH6aARGXOWE04E~TSLH37t~R3MrhSd~QBDtTs3QeTEjp6LhSuvjnjGMvxykTOTL7XpPqqQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"A_stochastic_model_of_hippocampal_synaptic_plasticity_with_geometrical_readout_of_enzyme_dynamics","translated_slug":"","page_count":47,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":86987972,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987972/thumbnails/1.jpg","file_name":"2021.03.30.437703.full.pdf","download_url":"https://www.academia.edu/attachments/86987972/download_file?st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"A_stochastic_model_of_hippocampal_synapt.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987972/2021.03.30.437703.full-libre.pdf?1654361892=\u0026response-content-disposition=attachment%3B+filename%3DA_stochastic_model_of_hippocampal_synapt.pdf\u0026Expires=1732417379\u0026Signature=hS6a6vZA6RrczqOlCmqbi2dTu2i0recqixmBHf0DhfcX~QQkX3qLW5O2-XOV8Jka5GWiIpzwjayHN0KDOqbA4bQ7knJcnJR4nfbmYFRY2wnYmMyncj7WP-dzk4sty2A4n3~D2nJVluQ8InER6Shk1Ig56azyPgeGHRsSumCOOFKYjCRZiN0zOWjXVyvlsRR24GFHwDEGAw9OLgoE2EGBDCAjLRwnb3VXtjrir~KtfePzxxaemk7GMMTgTTp9JBC5pd2LSGIJ65HG~FrXLH6aARGXOWE04E~TSLH37t~R3MrhSd~QBDtTs3QeTEjp6LhSuvjnjGMvxykTOTL7XpPqqQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"},{"id":32003,"name":"Synaptic Plasticity","url":"https://www.academia.edu/Documents/in/Synaptic_Plasticity"},{"id":174673,"name":"Preparation","url":"https://www.academia.edu/Documents/in/Preparation"}],"urls":[{"id":21091487,"url":"https://syndication.highwire.org/content/doi/10.1101/2021.03.30.437703"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80688179"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80688179/PURE_LET_denoising_code_PURE_LET_denoising_code_purelet_tbx_Help_Report_files"><img alt="Research paper thumbnail of PURE-LET denoising code/PURE-LET denoising code/purelet_tbx/Help Report_files" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688179/PURE_LET_denoising_code_PURE_LET_denoising_code_purelet_tbx_Help_Report_files">PURE-LET denoising code/PURE-LET denoising code/purelet_tbx/Help Report_files</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">MATLAB code for PURE-LET denoising of spine calcium transients</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688179"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688179"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688179; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80688178"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80688178/Spine_calcium_model"><img alt="Research paper thumbnail of Spine calcium model" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688178/Spine_calcium_model">Spine calcium model</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">MATLAB code for spine calcium model</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688178"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688178"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688178; 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80688177"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80688177/Modulation_of_ERK1_MAPK3_potentiates_ERK_nuclear_signalling_facilitates_neuronal_cell_survival_and_improves_memory_in_mouse_models_of_neurodegenerative_disorders"><img alt="Research paper thumbnail of Modulation of ERK1/MAPK3 potentiates ERK nuclear signalling, facilitates neuronal cell survival and improves memory in mouse models of neurodegenerative disorders" class="work-thumbnail" src="https://attachments.academia-assets.com/86987968/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688177/Modulation_of_ERK1_MAPK3_potentiates_ERK_nuclear_signalling_facilitates_neuronal_cell_survival_and_improves_memory_in_mouse_models_of_neurodegenerative_disorders">Modulation of ERK1/MAPK3 potentiates ERK nuclear signalling, facilitates neuronal cell survival and improves memory in mouse models of neurodegenerative disorders</a></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead to n...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead to neurodegenerative processes and associated cognitive decline. So far, a major effort has been directed toward the dissection of disease specific pathways with the still unmet promise to develop precision medicine strategies. With a different approach, here we show that a selective genetic potentiation of neuronal ERK signalling prevents cell death in vitro and in vivo in the mouse brain while ERK attenuation does the opposite. This neuroprotective effect can also be induced pharmacologically by a cell permeable peptide mimicking the loss of ERK1 MAP kinase, leading to a selective enhancement of ERK2 mediated nuclear cell signalling. The drug treatment prevents neurodegeneration in mouse models of Huntington&#39;s (HD), Alzheimer&#39;s (AD), and Parkinson&#39;s disease (PD). Importantly, the selective potentiation of ERK2 signalling facilitates both structural and synaptic plasticity, enha...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="8161d8034f51ddf3399b0bcfee02038d" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":86987968,"asset_id":80688177,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/86987968/download_file?st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688177"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688177"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688177; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80688177]").text(description); $(".js-view-count[data-work-id=80688177]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80688177; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80688177']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 80688177, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "8161d8034f51ddf3399b0bcfee02038d" } } $('.js-work-strip[data-work-id=80688177]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80688177,"title":"Modulation of ERK1/MAPK3 potentiates ERK nuclear signalling, facilitates neuronal cell survival and improves memory in mouse models of neurodegenerative disorders","translated_title":"","metadata":{"abstract":"Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead to neurodegenerative processes and associated cognitive decline. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80688175"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80688175/Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus"><img alt="Research paper thumbnail of Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus" class="work-thumbnail" src="https://attachments.academia-assets.com/86987964/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688175/Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus">Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 21, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we desc...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ad4d00523fe78f27820280e8a9c60c6e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":86987964,"asset_id":80688175,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/86987964/download_file?st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688175"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688175"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688175; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80688175]").text(description); $(".js-view-count[data-work-id=80688175]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80688175; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80688175']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 80688175, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ad4d00523fe78f27820280e8a9c60c6e" } } $('.js-work-strip[data-work-id=80688175]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80688175,"title":"Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus","translated_title":"","metadata":{"abstract":"Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we desc...","publication_date":{"day":21,"month":1,"year":2018,"errors":{}},"publication_name":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},"translated_abstract":"Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="67513697"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/67513697/Neurotrophin_receptor_activation_rescues_cognitive_and_synaptic_abnormalities_caused_by_hemizygosity_of_the_psychiatric_risk_gene_Cacna1c"><img alt="Research paper thumbnail of Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c" class="work-thumbnail" src="https://attachments.academia-assets.com/78300739/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/67513697/Neurotrophin_receptor_activation_rescues_cognitive_and_synaptic_abnormalities_caused_by_hemizygosity_of_the_psychiatric_risk_gene_Cacna1c">Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c</a></div><div class="wp-workCard_item"><span>Molecular Psychiatry</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated ca...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous for Cacna1c harbour marked impairments in learning to disregard non-salient stimuli, a behavioural change previously associated with psychosis. This behavioural deficit is accompanied by dys-coordinated network oscillations during learning, pathway-selective disruption of hippocampal synaptic plasticity, attenuated Ca2+ signalling in dendritic spines and decreased signalling through the Extracellular-signal Regulated Kinase (ERK) pathway. 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class="wp-workCard_item"><span>The Journal of Neuroscience 23 Pp 2323 2332</span><span>, 2003</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d892a42e2c918a1bb94d296b701eb951" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478716,"asset_id":31045306,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478716/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045306"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span 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for the acute disruption of synaptic AMPAR stabilization" class="work-thumbnail" src="https://attachments.academia-assets.com/51478713/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045305/Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization">Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization</a></div><div class="wp-workCard_item"><span>Nat Chem Biol</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="415a72e37b7e9966f768210a460f7dd6" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "415a72e37b7e9966f768210a460f7dd6" } } $('.js-work-strip[data-work-id=31045305]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045305,"title":"Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization","translated_title":"","metadata":{"grobid_abstract":"The user has requested enhancement of the downloaded file. All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Nat Chem Biol","grobid_abstract_attachment_id":51478713},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045305/Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization","translated_internal_url":"","created_at":"2017-01-23T03:27:13.355-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":51478713,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478713/thumbnails/1.jpg","file_name":"Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz.pdf","download_url":"https://www.academia.edu/attachments/51478713/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Biomimetic_divalent_ligands_for_the_acut.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478713/Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz-libre.pdf?1485171142=\u0026response-content-disposition=attachment%3B+filename%3DBiomimetic_divalent_ligands_for_the_acut.pdf\u0026Expires=1732417380\u0026Signature=cGlzreX97DPoAKOBs7GieMG5rPtn7ubC4CgtDergDr0UljGsJdcmbZ2m1ajxiohAXIWQK1J~RHHy7Y53GQrljK~jNHBhKT-96NHPPPpLwFtLND7n-a0~IIa6Bo2E2QZ~PM-~qMxFAaPx9EgpiDWPlqdzArOey2Vu5W1et0SNp4-vPTSVrxMCicFpUmZQr4b3FthuVSZsfOLuWSaszp73U2Q24pD700Dnril~6sBf~rqxTnw7v4SlEXLwZb~Zf8th9ojdDfHavL7bjAaqOzlZ-NfUoHfv1Eshr2iSUcYFlaZON9aV5F0awLq3Ow8w2untlE1DWUVf4ZjkT~Ml98f1rA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization","translated_slug":"","page_count":12,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478713,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478713/thumbnails/1.jpg","file_name":"Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz.pdf","download_url":"https://www.academia.edu/attachments/51478713/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Biomimetic_divalent_ligands_for_the_acut.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478713/Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz-libre.pdf?1485171142=\u0026response-content-disposition=attachment%3B+filename%3DBiomimetic_divalent_ligands_for_the_acut.pdf\u0026Expires=1732417380\u0026Signature=cGlzreX97DPoAKOBs7GieMG5rPtn7ubC4CgtDergDr0UljGsJdcmbZ2m1ajxiohAXIWQK1J~RHHy7Y53GQrljK~jNHBhKT-96NHPPPpLwFtLND7n-a0~IIa6Bo2E2QZ~PM-~qMxFAaPx9EgpiDWPlqdzArOey2Vu5W1et0SNp4-vPTSVrxMCicFpUmZQr4b3FthuVSZsfOLuWSaszp73U2Q24pD700Dnril~6sBf~rqxTnw7v4SlEXLwZb~Zf8th9ojdDfHavL7bjAaqOzlZ-NfUoHfv1Eshr2iSUcYFlaZON9aV5F0awLq3Ow8w2untlE1DWUVf4ZjkT~Ml98f1rA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":5467,"name":"Biomimetics","url":"https://www.academia.edu/Documents/in/Biomimetics"},{"id":418263,"name":"SYNAPSES","url":"https://www.academia.edu/Documents/in/SYNAPSES"},{"id":1222191,"name":"Ligands","url":"https://www.academia.edu/Documents/in/Ligands"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"}],"urls":[{"id":7902953,"url":"http://dx.doi.org/10.1038/nchembio.498"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045304"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus"><img alt="Research paper thumbnail of The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus: Post-synaptic density complexity and spine shape in the dentate gyrus" class="work-thumbnail" src="https://attachments.academia-assets.com/51478717/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus">The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus: Post-synaptic density complexity and spine shape in the dentate gyrus</a></div><div class="wp-workCard_item"><span>European Journal of Neuroscience</span><span>, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0dd6cdba658d0e53c2378b8058444bc2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478717,"asset_id":31045304,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045304"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045304"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045304; 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In knock-out (KO) mice the absence of GluR2 results in consequences for synaptic plasticity including cognitive impairments. Here the morphology of dendritic spines and their synaptic contacts was analysed via three-dimensional reconstruction of serial electron micrographs from dentate gyrus (DG) of adult wild type (WT) and GluR2 KO mice. Pre-embedding immunocytochemical staining was used to examine the distribution and subcellular localization of AMPA receptor GluR1 and N-methyl-d-aspartate receptor NR1 subunits. There were no significant changes in synapse density in the DG of GluR2 KO compared with WT mice. However, in GluR2 KO mice there was a significant decrease in the percentage of synapses on mushroom spines but an increase in synapses on thin spines. There was also a large decrease in the proportion of synapses with complex perforated ⁄ segmented post-synaptic densities (PSDs) (25 vs. 78% in WT) but an increase in synapses with macular PSDs (75 vs. 22%). These data were coupled in GluR2 KO mice with significant decreases in volume and surface area of mushroom spines and their PSDs. In both GluR2 KO and WT mice, NR1 and GluR1 receptors were present in dendrites and spines but there was a significant reduction in NR1 labelling of spine membranes and cytoplasm in GluR2 KO mice, and a small decrease in GluR1 immunolabelling in membranes and cytoplasm of spines in GluR2 KO compared with WT mice. Our data demonstrate that the absence of GluR2 has a significant effect on both DG synapse and spine cytoarchitecture and the expression of NR1 receptors.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"European Journal of Neuroscience","grobid_abstract_attachment_id":51478717},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus","translated_internal_url":"","created_at":"2017-01-23T03:27:11.816-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":51478717,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478717/thumbnails/1.jpg","file_name":"j.1460-9568.2007.06005.x20170123-25566-7whspa.pdf","download_url":"https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_glutamate_receptor_2_subunit_control.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478717/j.1460-9568.2007.06005.x20170123-25566-7whspa-libre.pdf?1485171114=\u0026response-content-disposition=attachment%3B+filename%3DThe_glutamate_receptor_2_subunit_control.pdf\u0026Expires=1732417380\u0026Signature=MmmXZBU8llnBovjC1eLIpLaq6xcxIGblReJbP9~ODi6MfLiYFiDx33rmwGgjZx~a7rDIbhhJbzUVvYOuJI3Pmp4jzXSC-1ITHg07jB2zU90DgN00wKYRZNwnepQUoKLa72OTGiz3K1Zrcg3KxyzZIVyBSllt3WNxSfjyiKgCUHRYoYL9BMYajGQJbGTztc5xB69rWK~Tkv1YZrFHhBL6DENm6RDwWbhGQrL53jbzpZpc4FR8Ux~qtNdJcWdn93y~LLV2urne0kXdTwnZBVGwm8hQIz227NWTsm-5-KGB0xYhNEbahqsWAMPH0h92MKpyHZbd5oRKtJ89Ow9xuXlVjg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus","translated_slug":"","page_count":11,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478717,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478717/thumbnails/1.jpg","file_name":"j.1460-9568.2007.06005.x20170123-25566-7whspa.pdf","download_url":"https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_glutamate_receptor_2_subunit_control.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478717/j.1460-9568.2007.06005.x20170123-25566-7whspa-libre.pdf?1485171114=\u0026response-content-disposition=attachment%3B+filename%3DThe_glutamate_receptor_2_subunit_control.pdf\u0026Expires=1732417380\u0026Signature=MmmXZBU8llnBovjC1eLIpLaq6xcxIGblReJbP9~ODi6MfLiYFiDx33rmwGgjZx~a7rDIbhhJbzUVvYOuJI3Pmp4jzXSC-1ITHg07jB2zU90DgN00wKYRZNwnepQUoKLa72OTGiz3K1Zrcg3KxyzZIVyBSllt3WNxSfjyiKgCUHRYoYL9BMYajGQJbGTztc5xB69rWK~Tkv1YZrFHhBL6DENm6RDwWbhGQrL53jbzpZpc4FR8Ux~qtNdJcWdn93y~LLV2urne0kXdTwnZBVGwm8hQIz227NWTsm-5-KGB0xYhNEbahqsWAMPH0h92MKpyHZbd5oRKtJ89Ow9xuXlVjg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology"},{"id":237,"name":"Cognitive Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science"},{"id":63466,"name":"Dendritic Spines","url":"https://www.academia.edu/Documents/in/Dendritic_Spines"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":111545,"name":"Male","url":"https://www.academia.edu/Documents/in/Male"},{"id":246876,"name":"Dentate Gyrus","url":"https://www.academia.edu/Documents/in/Dentate_Gyrus"},{"id":279027,"name":"European","url":"https://www.academia.edu/Documents/in/European"},{"id":418263,"name":"SYNAPSES","url":"https://www.academia.edu/Documents/in/SYNAPSES"},{"id":1239755,"name":"Neurosciences","url":"https://www.academia.edu/Documents/in/Neurosciences"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation"},{"id":1804048,"name":"AMPA receptors","url":"https://www.academia.edu/Documents/in/AMPA_receptors"},{"id":2012816,"name":"Glutamate Receptor","url":"https://www.academia.edu/Documents/in/Glutamate_Receptor"}],"urls":[{"id":7902952,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=20012981"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045302"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045302/Subcellular_localisation_of_recombinant_a_and_synuclein"><img alt="Research paper thumbnail of Subcellular localisation of recombinant a- and ?-synuclein" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045302/Subcellular_localisation_of_recombinant_a_and_synuclein">Subcellular localisation of recombinant a- and ?-synuclein</a></div><div class="wp-workCard_item"><span>Mol Cell Neurosci</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological func...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. However, γ-synuclein lacks a C-terminal domain that causes nuclear localisation of the fusion protein, suggesting that the two synucleins might have different roles relating to the cell nucleus.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045302"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045302"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045302; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045302]").text(description); $(".js-view-count[data-work-id=31045302]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045302; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045302']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045302, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045302]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045302,"title":"Subcellular localisation of recombinant a- and ?-synuclein","translated_title":"","metadata":{"abstract":"α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. However, γ-synuclein lacks a C-terminal domain that causes nuclear localisation of the fusion protein, suggesting that the two synucleins might have different roles relating to the cell nucleus.","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Mol Cell Neurosci"},"translated_abstract":"α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045297"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors"><img alt="Research paper thumbnail of Clathrin-independent trafficking of AMPA receptors" class="work-thumbnail" src="https://attachments.academia-assets.com/51478712/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors">Clathrin-independent trafficking of AMPA receptors</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 25, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity....</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ee358b3de8106d7dc3f5684e01c05439" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478712,"asset_id":31045297,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045297"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045297"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045297; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045297]").text(description); $(".js-view-count[data-work-id=31045297]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045297; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045297']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045297, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ee358b3de8106d7dc3f5684e01c05439" } } $('.js-work-strip[data-work-id=31045297]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045297,"title":"Clathrin-independent trafficking of AMPA receptors","translated_title":"","metadata":{"abstract":"Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.","publication_date":{"day":25,"month":1,"year":2015,"errors":{}},"publication_name":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},"translated_abstract":"Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.","internal_url":"https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors","translated_internal_url":"","created_at":"2017-01-23T03:27:07.929-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":28533068,"work_id":31045297,"tagging_user_id":1844143,"tagged_user_id":59323581,"co_author_invite_id":null,"email":"j***r@bristol.ac.uk","display_order":4194304,"name":"Jack Mellor","title":"Clathrin-independent trafficking of AMPA receptors"},{"id":28533069,"work_id":31045297,"tagging_user_id":1844143,"tagged_user_id":null,"co_author_invite_id":5777376,"email":"a***g@bristol.ac.uk","display_order":6291456,"name":"Oleg Glebov","title":"Clathrin-independent trafficking of AMPA receptors"}],"downloadable_attachments":[{"id":51478712,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478712/thumbnails/1.jpg","file_name":"4830.full.pdf","download_url":"https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Clathrin_independent_trafficking_of_AMPA.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478712/4830.full-libre.pdf?1485171118=\u0026response-content-disposition=attachment%3B+filename%3DClathrin_independent_trafficking_of_AMPA.pdf\u0026Expires=1732417380\u0026Signature=Q7uz5Du3WPgEmGbNGAHp6D0PmTryHEATOv5yaDJV0HGErEGvNzDIG-Y~fJqHTSv5jihlZaLjggmbVneEFJ2QS2vuZEVEbBOiL~tS0vpFZj5mehk~-ms6VwXLuUkCQkeUvg0Vyq9WuHo10FN6Z4l5XK3nqct~tEPvSkklfOfxZcnhLa9Oqx-qGhiaA4vxlMmnCF9MMhDg3fbwFT~ni4dTZ4p-SHK2ZSkXPDbhAqNADHrmu9TWhWk5DykuBidjemCpTxFUATHJMvdQjta-7RWK11l3ctTjkARrijsIZxBxsfoJ0h4FKR6MYDxkw66yf7fdLi388ihYqp841AmCmVbU9w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Clathrin_independent_trafficking_of_AMPA_receptors","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478712,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478712/thumbnails/1.jpg","file_name":"4830.full.pdf","download_url":"https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Clathrin_independent_trafficking_of_AMPA.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478712/4830.full-libre.pdf?1485171118=\u0026response-content-disposition=attachment%3B+filename%3DClathrin_independent_trafficking_of_AMPA.pdf\u0026Expires=1732417380\u0026Signature=Q7uz5Du3WPgEmGbNGAHp6D0PmTryHEATOv5yaDJV0HGErEGvNzDIG-Y~fJqHTSv5jihlZaLjggmbVneEFJ2QS2vuZEVEbBOiL~tS0vpFZj5mehk~-ms6VwXLuUkCQkeUvg0Vyq9WuHo10FN6Z4l5XK3nqct~tEPvSkklfOfxZcnhLa9Oqx-qGhiaA4vxlMmnCF9MMhDg3fbwFT~ni4dTZ4p-SHK2ZSkXPDbhAqNADHrmu9TWhWk5DykuBidjemCpTxFUATHJMvdQjta-7RWK11l3ctTjkARrijsIZxBxsfoJ0h4FKR6MYDxkw66yf7fdLi388ihYqp841AmCmVbU9w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":111545,"name":"Male","url":"https://www.academia.edu/Documents/in/Male"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons"},{"id":362533,"name":"Hydrazones","url":"https://www.academia.edu/Documents/in/Hydrazones"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":1457054,"name":"Protein Transport","url":"https://www.academia.edu/Documents/in/Protein_Transport"},{"id":1549061,"name":"Clathrin","url":"https://www.academia.edu/Documents/in/Clathrin"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045296"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_"><img alt="Research paper thumbnail of [Molecular mechanism of tolerance for vasodilator nitrates]" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_">[Molecular mechanism of tolerance for vasodilator nitrates]</a></div><div class="wp-workCard_item"><span>Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045296"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045296"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045296; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045296]").text(description); $(".js-view-count[data-work-id=31045296]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045296; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045296']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045296, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045296]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045296,"title":"[Molecular mechanism of tolerance for vasodilator nitrates]","translated_title":"","metadata":{"publication_name":"Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă"},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_","translated_internal_url":"","created_at":"2017-01-23T03:27:07.162-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":28533071,"work_id":31045296,"tagging_user_id":1844143,"tagged_user_id":32831476,"co_author_invite_id":null,"email":"s***u@gmail.com","affiliation":"University of Bucharest","display_order":0,"name":"Stefan Constantinescu","title":"[Molecular mechanism of tolerance for vasodilator nitrates]"},{"id":28533072,"work_id":31045296,"tagging_user_id":1844143,"tagged_user_id":37893974,"co_author_invite_id":null,"email":"m***u@yahoo.com","display_order":4194304,"name":"Mihail Hinescu","title":"[Molecular mechanism of tolerance for vasodilator nitrates]"}],"downloadable_attachments":[],"slug":"_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[],"research_interests":[{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":99271,"name":"Calcium channels","url":"https://www.academia.edu/Documents/in/Calcium_channels"},{"id":122402,"name":"Nitrates","url":"https://www.academia.edu/Documents/in/Nitrates"},{"id":419370,"name":"Swine","url":"https://www.academia.edu/Documents/in/Swine"},{"id":1592853,"name":"Drug Tolerance","url":"https://www.academia.edu/Documents/in/Drug_Tolerance"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045295"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045295/Decreased_alpha_1_adrenergic_receptors_after_experimental_brain_injury"><img alt="Research paper thumbnail of Decreased alpha 1-adrenergic receptors after experimental brain injury" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045295/Decreased_alpha_1_adrenergic_receptors_after_experimental_brain_injury">Decreased alpha 1-adrenergic receptors after experimental brain injury</a></div><div class="wp-workCard_item"><span>Journal of neurotrauma</span><span>, 1992</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p &lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of le...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045295"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045295"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045295; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045295]").text(description); $(".js-view-count[data-work-id=31045295]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045295; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045295']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045295, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045295]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045295,"title":"Decreased alpha 1-adrenergic receptors after experimental brain injury","translated_title":"","metadata":{"abstract":"The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p \u0026lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of le...","publication_date":{"day":null,"month":null,"year":1992,"errors":{}},"publication_name":"Journal of neurotrauma"},"translated_abstract":"The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p \u0026lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. 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In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NM...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="790ec9fdd336c118de52ddfbc22a4a05" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478715,"asset_id":31045294,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478715/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045294"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045294"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045294; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045294]").text(description); $(".js-view-count[data-work-id=31045294]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045294; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045294']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045294, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "790ec9fdd336c118de52ddfbc22a4a05" } } $('.js-work-strip[data-work-id=31045294]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045294,"title":"Absence of Whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling","translated_title":"","metadata":{"abstract":"Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+ block might play a special role. In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NM...","publication_date":{"day":15,"month":1,"year":2003,"errors":{}},"publication_name":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},"translated_abstract":"Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+ block might play a special role. In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. 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of Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients" class="work-thumbnail" src="https://attachments.academia-assets.com/108769205/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/109504767/Wavelet_Transform_Based_De_Noising_for_Two_Photon_Imaging_of_Synaptic_Ca_2_Transients">Wavelet Transform-Based De-Noising for Two-Photon Imaging of Synaptic Ca 2+ Transients</a></div><div class="wp-workCard_item"><span>Biophysical Journal</span><span>, Mar 1, 2013</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="c27e78fc45b85874a793e9cc9ec936ac" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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Existing plasticity models are either 1) top-down and interpretable, but not flexible enough to account for experimental data, or 2) bottom-up and biologically realistic, but too intricate to interpret and hard to fit to data. We fill the gap between these approaches by uncovering a new plasticity rule based on a geometrical readout mechanism that flexibly maps synaptic enzyme dynamics to plasticity outcomes. We apply this readout to a multi-timescale model of hippocampal synaptic plasticity induction that includes electrical dynamics, calcium, CaMKII and calcineurin, and accurate representation of intrinsic noise sources. Using a single set of model parameters, we demonstrate the robustness of this plasticity rule by reproducing nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental condit...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="1396cab7f16772f71892fe6191d17a0a" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":86987972,"asset_id":80688180,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/86987972/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688180"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688180"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688180; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80688180]").text(description); $(".js-view-count[data-work-id=80688180]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80688180; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80688180']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 80688180, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "1396cab7f16772f71892fe6191d17a0a" } } $('.js-work-strip[data-work-id=80688180]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80688180,"title":"A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics","translated_title":"","metadata":{"abstract":"Discovering the rules of synaptic plasticity is an important step for understanding brain learning. 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So far, a major effort has been directed toward the dissection of disease specific pathways with the still unmet promise to develop precision medicine strategies. With a different approach, here we show that a selective genetic potentiation of neuronal ERK signalling prevents cell death in vitro and in vivo in the mouse brain while ERK attenuation does the opposite. This neuroprotective effect can also be induced pharmacologically by a cell permeable peptide mimicking the loss of ERK1 MAP kinase, leading to a selective enhancement of ERK2 mediated nuclear cell signalling. The drug treatment prevents neurodegeneration in mouse models of Huntington&#39;s (HD), Alzheimer&#39;s (AD), and Parkinson&#39;s disease (PD). 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Importantly, the selective potentiation of ERK2 signalling facilitates both structural and synaptic plasticity, enha...","internal_url":"https://www.academia.edu/80688177/Modulation_of_ERK1_MAPK3_potentiates_ERK_nuclear_signalling_facilitates_neuronal_cell_survival_and_improves_memory_in_mouse_models_of_neurodegenerative_disorders","translated_internal_url":"","created_at":"2022-06-04T09:42:09.629-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":86987968,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987968/thumbnails/1.jpg","file_name":"496141.full.pdf","download_url":"https://www.academia.edu/attachments/86987968/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Modulation_of_ERK1_MAPK3_potentiates_ERK.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987968/496141.full-libre.pdf?1654361870=\u0026response-content-disposition=attachment%3B+filename%3DModulation_of_ERK1_MAPK3_potentiates_ERK.pdf\u0026Expires=1732417379\u0026Signature=VtPudK1ruPagqw4dQCPRkhEkbj9QKsrjNbLdp4sRCN~XW6bUYn-B4atWbJhujC55l48jUFa4q7k5sfZe1UKLvI65sNUZvUAQTxsUD9HCwA6CMPVQ6TK24Acuu-rK-Ro4cmQ7dVwyNHQD6xcOAJnTRVT64Y7~dHgI03fZjlJGuhoA2au3tcGSSfefx74ekBUj8k9YbI9vfY1dhD-RuUyqWzEr1pGaOexY~vQyNUlBgI6uGjgDzOHclGv9z-g9CR9abtzbMzYgLxDN0E3T33K8IDAgZcyYsMbSIwdRTNJ02ZeWbh3K4Sf914DHqRSNKGM6c3NwmJDQ1MHE3UcBzoA7jQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Modulation_of_ERK1_MAPK3_potentiates_ERK_nuclear_signalling_facilitates_neuronal_cell_survival_and_improves_memory_in_mouse_models_of_neurodegenerative_disorders","translated_slug":"","page_count":33,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":86987968,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987968/thumbnails/1.jpg","file_name":"496141.full.pdf","download_url":"https://www.academia.edu/attachments/86987968/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Modulation_of_ERK1_MAPK3_potentiates_ERK.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987968/496141.full-libre.pdf?1654361870=\u0026response-content-disposition=attachment%3B+filename%3DModulation_of_ERK1_MAPK3_potentiates_ERK.pdf\u0026Expires=1732417379\u0026Signature=VtPudK1ruPagqw4dQCPRkhEkbj9QKsrjNbLdp4sRCN~XW6bUYn-B4atWbJhujC55l48jUFa4q7k5sfZe1UKLvI65sNUZvUAQTxsUD9HCwA6CMPVQ6TK24Acuu-rK-Ro4cmQ7dVwyNHQD6xcOAJnTRVT64Y7~dHgI03fZjlJGuhoA2au3tcGSSfefx74ekBUj8k9YbI9vfY1dhD-RuUyqWzEr1pGaOexY~vQyNUlBgI6uGjgDzOHclGv9z-g9CR9abtzbMzYgLxDN0E3T33K8IDAgZcyYsMbSIwdRTNJ02ZeWbh3K4Sf914DHqRSNKGM6c3NwmJDQ1MHE3UcBzoA7jQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":7710,"name":"Biology","url":"https://www.academia.edu/Documents/in/Biology"}],"urls":[{"id":21091486,"url":"https://syndication.highwire.org/content/doi/10.1101/496141"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="80688175"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/80688175/Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus"><img alt="Research paper thumbnail of Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus" class="work-thumbnail" src="https://attachments.academia-assets.com/86987964/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/80688175/Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus">Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 21, 2018</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by p...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we desc...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ad4d00523fe78f27820280e8a9c60c6e" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":86987964,"asset_id":80688175,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/86987964/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="80688175"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="80688175"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 80688175; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=80688175]").text(description); $(".js-view-count[data-work-id=80688175]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 80688175; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='80688175']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 80688175, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ad4d00523fe78f27820280e8a9c60c6e" } } $('.js-work-strip[data-work-id=80688175]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":80688175,"title":"Convergent metabotropic signalling pathways inhibit SK channels to promote synaptic plasticity in the hippocampus","translated_title":"","metadata":{"abstract":"Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we desc...","publication_date":{"day":21,"month":1,"year":2018,"errors":{}},"publication_name":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},"translated_abstract":"Hebbian synaptic plasticity at hippocampal Schaffer collateral synapses is tightly regulated by postsynaptic SK channels that restrict NMDA receptor activity. SK channels are themselves modulated by G-protein-coupled signalling pathways, but it is not clear under what conditions these are activated to enable synaptic plasticity. Here, we show that muscarinic M1 receptor (M1R) and type 1 metabotropic glutamate receptor (mGluR1) signalling pathways, which are known to inhibit SK channels and thereby disinhibit NMDA receptors, converge to facilitate spine calcium transients during the induction of long-term potentiation (LTP) at hippocampal Schaffer collateral synapses onto CA1 pyramidal neurons of male rats. Furthermore, mGluR1 activation is required for LTP induced by reactivated place cell firing patterns that occur in sharp wave ripple events during rest or sleep. In contrast, M1R activation is required for LTP induced by place cell firing patterns during exploration. Thus, we desc...","internal_url":"https://www.academia.edu/80688175/Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus","translated_internal_url":"","created_at":"2022-06-04T09:42:09.521-07:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":86987964,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987964/thumbnails/1.jpg","file_name":"Tigaret_20Mellor_202018.pdf","download_url":"https://www.academia.edu/attachments/86987964/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Convergent_metabotropic_signalling_pathw.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987964/Tigaret_20Mellor_202018-libre.pdf?1654361842=\u0026response-content-disposition=attachment%3B+filename%3DConvergent_metabotropic_signalling_pathw.pdf\u0026Expires=1732417379\u0026Signature=Q8vOfvVYNTC37H-Noh7ZOrbv5j65cNrlcA-sxkwfH~IQouDahNTP7CG-bXIy~sCMxOnIKSHVLCyIBf03S-aGBoAB~Hk83Kp2bm4M73TiZkBg~ptcwxc8Xmn8JcJ0RfXVbmK98jBhz7NHwCndldwJGv8LxS3FZbpbzG3dcSZv4zh2tHN4O9WayklGmJApxGA0uEPJ38mUs4o9xSYi3X3kLfCJRl3SA-5ASAmOg1ZH4NVda1tkF3ceBL2H0VHuhmJ4LUP~UsiQx8qSilA1dLdSFmAVenfXluHgVXFQ6bJ4AuOOfM8CbJtOKdlEMBrFdWkicSd0p5a1YAaJM2rxyQEchA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Convergent_metabotropic_signalling_pathways_inhibit_SK_channels_to_promote_synaptic_plasticity_in_the_hippocampus","translated_slug":"","page_count":11,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":86987964,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/86987964/thumbnails/1.jpg","file_name":"Tigaret_20Mellor_202018.pdf","download_url":"https://www.academia.edu/attachments/86987964/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc3OSw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Convergent_metabotropic_signalling_pathw.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/86987964/Tigaret_20Mellor_202018-libre.pdf?1654361842=\u0026response-content-disposition=attachment%3B+filename%3DConvergent_metabotropic_signalling_pathw.pdf\u0026Expires=1732417379\u0026Signature=Q8vOfvVYNTC37H-Noh7ZOrbv5j65cNrlcA-sxkwfH~IQouDahNTP7CG-bXIy~sCMxOnIKSHVLCyIBf03S-aGBoAB~Hk83Kp2bm4M73TiZkBg~ptcwxc8Xmn8JcJ0RfXVbmK98jBhz7NHwCndldwJGv8LxS3FZbpbzG3dcSZv4zh2tHN4O9WayklGmJApxGA0uEPJ38mUs4o9xSYi3X3kLfCJRl3SA-5ASAmOg1ZH4NVda1tkF3ceBL2H0VHuhmJ4LUP~UsiQx8qSilA1dLdSFmAVenfXluHgVXFQ6bJ4AuOOfM8CbJtOKdlEMBrFdWkicSd0p5a1YAaJM2rxyQEchA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":523,"name":"Chemistry","url":"https://www.academia.edu/Documents/in/Chemistry"},{"id":4247,"name":"Long Term Potentiation","url":"https://www.academia.edu/Documents/in/Long_Term_Potentiation"},{"id":26327,"name":"Medicine","url":"https://www.academia.edu/Documents/in/Medicine"},{"id":32003,"name":"Synaptic Plasticity","url":"https://www.academia.edu/Documents/in/Synaptic_Plasticity"},{"id":2922956,"name":"Psychology and Cognitive Sciences","url":"https://www.academia.edu/Documents/in/Psychology_and_Cognitive_Sciences"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"urls":[]}, dispatcherData: dispatcherData }); 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="67513697"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/67513697/Neurotrophin_receptor_activation_rescues_cognitive_and_synaptic_abnormalities_caused_by_hemizygosity_of_the_psychiatric_risk_gene_Cacna1c"><img alt="Research paper thumbnail of Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c" class="work-thumbnail" src="https://attachments.academia-assets.com/78300739/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/67513697/Neurotrophin_receptor_activation_rescues_cognitive_and_synaptic_abnormalities_caused_by_hemizygosity_of_the_psychiatric_risk_gene_Cacna1c">Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c</a></div><div class="wp-workCard_item"><span>Molecular Psychiatry</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated ca...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous for Cacna1c harbour marked impairments in learning to disregard non-salient stimuli, a behavioural change previously associated with psychosis. This behavioural deficit is accompanied by dys-coordinated network oscillations during learning, pathway-selective disruption of hippocampal synaptic plasticity, attenuated Ca2+ signalling in dendritic spines and decreased signalling through the Extracellular-signal Regulated Kinase (ERK) pathway. Activation of the ERK pathway by a small-molecule agonist of TrkB/TrkC neurotrophin...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="806b6348f920e111c6511e9db94670c9" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":78300739,"asset_id":67513697,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/78300739/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="67513697"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="67513697"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 67513697; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=67513697]").text(description); $(".js-view-count[data-work-id=67513697]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 67513697; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='67513697']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 67513697, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "806b6348f920e111c6511e9db94670c9" } } $('.js-work-strip[data-work-id=67513697]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":67513697,"title":"Neurotrophin receptor activation rescues cognitive and synaptic abnormalities caused by hemizygosity of the psychiatric risk gene Cacna1c","translated_title":"","metadata":{"abstract":"Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous for Cacna1c harbour marked impairments in learning to disregard non-salient stimuli, a behavioural change previously associated with psychosis. This behavioural deficit is accompanied by dys-coordinated network oscillations during learning, pathway-selective disruption of hippocampal synaptic plasticity, attenuated Ca2+ signalling in dendritic spines and decreased signalling through the Extracellular-signal Regulated Kinase (ERK) pathway. Activation of the ERK pathway by a small-molecule agonist of TrkB/TrkC neurotrophin...","publisher":"Springer Science and Business Media LLC","publication_name":"Molecular Psychiatry"},"translated_abstract":"Genetic variation in CACNA1C, which encodes the alpha-1 subunit of CaV1.2 L-type voltage-gated calcium channels, is strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder. To translate genetics to neurobiological mechanisms and rational therapeutic targets, we investigated the impact of mutations of one copy of Cacna1c on rat cognitive, synaptic and circuit phenotypes implicated by patient studies. We show that rats hemizygous for Cacna1c harbour marked impairments in learning to disregard non-salient stimuli, a behavioural change previously associated with psychosis. 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href="https://www.academia.edu/31045306/Absence_of_Whisker_Related_Pattern_Formation_in_Mice_with_NMDA_Receptors_Lacking_Coincidence_Detection_Properties_and_Calcium_Signaling"><img alt="Research paper thumbnail of Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling" class="work-thumbnail" src="https://attachments.academia-assets.com/51478716/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045306/Absence_of_Whisker_Related_Pattern_Formation_in_Mice_with_NMDA_Receptors_Lacking_Coincidence_Detection_Properties_and_Calcium_Signaling">Absence of Whisker-Related Pattern Formation in Mice with NMDA Receptors Lacking Coincidence Detection Properties and Calcium Signaling</a></div><div class="wp-workCard_item"><span>The Journal of Neuroscience 23 Pp 2323 2332</span><span>, 2003</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="d892a42e2c918a1bb94d296b701eb951" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478716,"asset_id":31045306,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478716/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045306"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa 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for the acute disruption of synaptic AMPAR stabilization" class="work-thumbnail" src="https://attachments.academia-assets.com/51478713/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045305/Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization">Biomimetic divalent ligands for the acute disruption of synaptic AMPAR stabilization</a></div><div class="wp-workCard_item"><span>Nat Chem Biol</span><span>, 2010</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="415a72e37b7e9966f768210a460f7dd6" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" 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All in-text references underlined in blue are added to the original document and are linked to publications on ResearchGate, letting you access and read them immediately. The interactions of the AMPA receptor (AMPAR) auxiliary subunit Stargazin with PDZ domain-containing scaffold proteins such as PSD-95 are critical for the synaptic stabilization of AMPARs. To investigate these interactions, we have developed biomimetic competing ligands that are assembled from two Stargazin-derived PSD-95/DLG/ZO-1 (PDZ) domain-binding motifs using 'click' chemistry. Characterization of the ligands in vitro and in a cellular FRET-based model revealed an enhanced affinity for the multiple PDZ domains of PSD-95 compared to monovalent peptides. In cultured neurons, the divalent ligands competed with transmembrane AMPAR regulatory protein (TARP) for the intracellular membrane-associated guanylate kinase resulting in increased lateral diffusion and endocytosis of surface AMPARs, while showing strong inhibition of synaptic AMPAR currents. This provides evidence for a model in which the TARP-containing AMPARs are stabilized at the synapse by engaging in multivalent interactions. In light of the prevalence of PDZ domain clusters, these new biomimetic chemical tools could find broad application for acutely perturbing multivalent complexes.","publication_date":{"day":null,"month":null,"year":2010,"errors":{}},"publication_name":"Nat Chem Biol","grobid_abstract_attachment_id":51478713},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045305/Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization","translated_internal_url":"","created_at":"2017-01-23T03:27:13.355-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":51478713,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478713/thumbnails/1.jpg","file_name":"Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz.pdf","download_url":"https://www.academia.edu/attachments/51478713/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Biomimetic_divalent_ligands_for_the_acut.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478713/Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz-libre.pdf?1485171142=\u0026response-content-disposition=attachment%3B+filename%3DBiomimetic_divalent_ligands_for_the_acut.pdf\u0026Expires=1732417380\u0026Signature=cGlzreX97DPoAKOBs7GieMG5rPtn7ubC4CgtDergDr0UljGsJdcmbZ2m1ajxiohAXIWQK1J~RHHy7Y53GQrljK~jNHBhKT-96NHPPPpLwFtLND7n-a0~IIa6Bo2E2QZ~PM-~qMxFAaPx9EgpiDWPlqdzArOey2Vu5W1et0SNp4-vPTSVrxMCicFpUmZQr4b3FthuVSZsfOLuWSaszp73U2Q24pD700Dnril~6sBf~rqxTnw7v4SlEXLwZb~Zf8th9ojdDfHavL7bjAaqOzlZ-NfUoHfv1Eshr2iSUcYFlaZON9aV5F0awLq3Ow8w2untlE1DWUVf4ZjkT~Ml98f1rA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Biomimetic_divalent_ligands_for_the_acute_disruption_of_synaptic_AMPAR_stabilization","translated_slug":"","page_count":12,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478713,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478713/thumbnails/1.jpg","file_name":"Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz.pdf","download_url":"https://www.academia.edu/attachments/51478713/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Biomimetic_divalent_ligands_for_the_acut.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478713/Biomimetic_divalent_ligands_for_the_acut20170123-25566-yq6npz-libre.pdf?1485171142=\u0026response-content-disposition=attachment%3B+filename%3DBiomimetic_divalent_ligands_for_the_acut.pdf\u0026Expires=1732417380\u0026Signature=cGlzreX97DPoAKOBs7GieMG5rPtn7ubC4CgtDergDr0UljGsJdcmbZ2m1ajxiohAXIWQK1J~RHHy7Y53GQrljK~jNHBhKT-96NHPPPpLwFtLND7n-a0~IIa6Bo2E2QZ~PM-~qMxFAaPx9EgpiDWPlqdzArOey2Vu5W1et0SNp4-vPTSVrxMCicFpUmZQr4b3FthuVSZsfOLuWSaszp73U2Q24pD700Dnril~6sBf~rqxTnw7v4SlEXLwZb~Zf8th9ojdDfHavL7bjAaqOzlZ-NfUoHfv1Eshr2iSUcYFlaZON9aV5F0awLq3Ow8w2untlE1DWUVf4ZjkT~Ml98f1rA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":5467,"name":"Biomimetics","url":"https://www.academia.edu/Documents/in/Biomimetics"},{"id":418263,"name":"SYNAPSES","url":"https://www.academia.edu/Documents/in/SYNAPSES"},{"id":1222191,"name":"Ligands","url":"https://www.academia.edu/Documents/in/Ligands"},{"id":1681026,"name":"Biochemistry and cell biology","url":"https://www.academia.edu/Documents/in/Biochemistry_and_cell_biology"}],"urls":[{"id":7902953,"url":"http://dx.doi.org/10.1038/nchembio.498"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045304"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus"><img alt="Research paper thumbnail of The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus: Post-synaptic density complexity and spine shape in the dentate gyrus" class="work-thumbnail" src="https://attachments.academia-assets.com/51478717/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus">The glutamate receptor 2 subunit controls post-synaptic density complexity and spine shape in the dentate gyrus: Post-synaptic density complexity and spine shape in the dentate gyrus</a></div><div class="wp-workCard_item"><span>European Journal of Neuroscience</span><span>, 2008</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="0dd6cdba658d0e53c2378b8058444bc2" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478717,"asset_id":31045304,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045304"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045304"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045304; 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In knock-out (KO) mice the absence of GluR2 results in consequences for synaptic plasticity including cognitive impairments. Here the morphology of dendritic spines and their synaptic contacts was analysed via three-dimensional reconstruction of serial electron micrographs from dentate gyrus (DG) of adult wild type (WT) and GluR2 KO mice. Pre-embedding immunocytochemical staining was used to examine the distribution and subcellular localization of AMPA receptor GluR1 and N-methyl-d-aspartate receptor NR1 subunits. There were no significant changes in synapse density in the DG of GluR2 KO compared with WT mice. However, in GluR2 KO mice there was a significant decrease in the percentage of synapses on mushroom spines but an increase in synapses on thin spines. There was also a large decrease in the proportion of synapses with complex perforated ⁄ segmented post-synaptic densities (PSDs) (25 vs. 78% in WT) but an increase in synapses with macular PSDs (75 vs. 22%). These data were coupled in GluR2 KO mice with significant decreases in volume and surface area of mushroom spines and their PSDs. In both GluR2 KO and WT mice, NR1 and GluR1 receptors were present in dendrites and spines but there was a significant reduction in NR1 labelling of spine membranes and cytoplasm in GluR2 KO mice, and a small decrease in GluR1 immunolabelling in membranes and cytoplasm of spines in GluR2 KO compared with WT mice. Our data demonstrate that the absence of GluR2 has a significant effect on both DG synapse and spine cytoarchitecture and the expression of NR1 receptors.","publication_date":{"day":null,"month":null,"year":2008,"errors":{}},"publication_name":"European Journal of Neuroscience","grobid_abstract_attachment_id":51478717},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045304/The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus","translated_internal_url":"","created_at":"2017-01-23T03:27:11.816-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[],"downloadable_attachments":[{"id":51478717,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478717/thumbnails/1.jpg","file_name":"j.1460-9568.2007.06005.x20170123-25566-7whspa.pdf","download_url":"https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_glutamate_receptor_2_subunit_control.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478717/j.1460-9568.2007.06005.x20170123-25566-7whspa-libre.pdf?1485171114=\u0026response-content-disposition=attachment%3B+filename%3DThe_glutamate_receptor_2_subunit_control.pdf\u0026Expires=1732417380\u0026Signature=MmmXZBU8llnBovjC1eLIpLaq6xcxIGblReJbP9~ODi6MfLiYFiDx33rmwGgjZx~a7rDIbhhJbzUVvYOuJI3Pmp4jzXSC-1ITHg07jB2zU90DgN00wKYRZNwnepQUoKLa72OTGiz3K1Zrcg3KxyzZIVyBSllt3WNxSfjyiKgCUHRYoYL9BMYajGQJbGTztc5xB69rWK~Tkv1YZrFHhBL6DENm6RDwWbhGQrL53jbzpZpc4FR8Ux~qtNdJcWdn93y~LLV2urne0kXdTwnZBVGwm8hQIz227NWTsm-5-KGB0xYhNEbahqsWAMPH0h92MKpyHZbd5oRKtJ89Ow9xuXlVjg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"The_glutamate_receptor_2_subunit_controls_post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus_Post_synaptic_density_complexity_and_spine_shape_in_the_dentate_gyrus","translated_slug":"","page_count":11,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478717,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478717/thumbnails/1.jpg","file_name":"j.1460-9568.2007.06005.x20170123-25566-7whspa.pdf","download_url":"https://www.academia.edu/attachments/51478717/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"The_glutamate_receptor_2_subunit_control.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478717/j.1460-9568.2007.06005.x20170123-25566-7whspa-libre.pdf?1485171114=\u0026response-content-disposition=attachment%3B+filename%3DThe_glutamate_receptor_2_subunit_control.pdf\u0026Expires=1732417380\u0026Signature=MmmXZBU8llnBovjC1eLIpLaq6xcxIGblReJbP9~ODi6MfLiYFiDx33rmwGgjZx~a7rDIbhhJbzUVvYOuJI3Pmp4jzXSC-1ITHg07jB2zU90DgN00wKYRZNwnepQUoKLa72OTGiz3K1Zrcg3KxyzZIVyBSllt3WNxSfjyiKgCUHRYoYL9BMYajGQJbGTztc5xB69rWK~Tkv1YZrFHhBL6DENm6RDwWbhGQrL53jbzpZpc4FR8Ux~qtNdJcWdn93y~LLV2urne0kXdTwnZBVGwm8hQIz227NWTsm-5-KGB0xYhNEbahqsWAMPH0h92MKpyHZbd5oRKtJ89Ow9xuXlVjg__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology"},{"id":237,"name":"Cognitive Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science"},{"id":63466,"name":"Dendritic Spines","url":"https://www.academia.edu/Documents/in/Dendritic_Spines"},{"id":84760,"name":"Mice","url":"https://www.academia.edu/Documents/in/Mice"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":111545,"name":"Male","url":"https://www.academia.edu/Documents/in/Male"},{"id":246876,"name":"Dentate Gyrus","url":"https://www.academia.edu/Documents/in/Dentate_Gyrus"},{"id":279027,"name":"European","url":"https://www.academia.edu/Documents/in/European"},{"id":418263,"name":"SYNAPSES","url":"https://www.academia.edu/Documents/in/SYNAPSES"},{"id":1239755,"name":"Neurosciences","url":"https://www.academia.edu/Documents/in/Neurosciences"},{"id":1763968,"name":"Gene Expression Regulation","url":"https://www.academia.edu/Documents/in/Gene_Expression_Regulation"},{"id":1804048,"name":"AMPA receptors","url":"https://www.academia.edu/Documents/in/AMPA_receptors"},{"id":2012816,"name":"Glutamate Receptor","url":"https://www.academia.edu/Documents/in/Glutamate_Receptor"}],"urls":[{"id":7902952,"url":"http://cat.inist.fr/?aModele=afficheN\u0026cpsidt=20012981"}]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045302"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045302/Subcellular_localisation_of_recombinant_a_and_synuclein"><img alt="Research paper thumbnail of Subcellular localisation of recombinant a- and ?-synuclein" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045302/Subcellular_localisation_of_recombinant_a_and_synuclein">Subcellular localisation of recombinant a- and ?-synuclein</a></div><div class="wp-workCard_item"><span>Mol Cell Neurosci</span><span>, 2005</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological func...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. However, γ-synuclein lacks a C-terminal domain that causes nuclear localisation of the fusion protein, suggesting that the two synucleins might have different roles relating to the cell nucleus.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045302"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045302"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045302; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045302]").text(description); $(".js-view-count[data-work-id=31045302]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045302; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045302']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045302, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045302]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045302,"title":"Subcellular localisation of recombinant a- and ?-synuclein","translated_title":"","metadata":{"abstract":"α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. However, γ-synuclein lacks a C-terminal domain that causes nuclear localisation of the fusion protein, suggesting that the two synucleins might have different roles relating to the cell nucleus.","publication_date":{"day":null,"month":null,"year":2005,"errors":{}},"publication_name":"Mol Cell Neurosci"},"translated_abstract":"α-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained controversial. We expressed synuclein–eGFP fusion proteins in organotypic rat hippocampal slice cultures and murine hippocampal primary neurons using a Sindbis virus expression system. Recombinant full-length α-synuclein accumulated in presynaptic locations, mimicking its native distribution. Expression of deletion mutant α-synuclein revealed that presynaptic targeting depended on the presence of its N-terminal and core region. This domain also causes nuclear exclusion of the α-synuclein fusion protein. In contrast, the C-terminal domain of α-synuclein directs fusion proteins into the nuclear compartment. The related protein γ-synuclein contains a similar N-terminal and core domain as α-synuclein. 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$(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045297"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors"><img alt="Research paper thumbnail of Clathrin-independent trafficking of AMPA receptors" class="work-thumbnail" src="https://attachments.academia-assets.com/51478712/thumbnails/1.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors">Clathrin-independent trafficking of AMPA receptors</a></div><div class="wp-workCard_item"><span>The Journal of neuroscience : the official journal of the Society for Neuroscience</span><span>, Jan 25, 2015</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity....</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="ee358b3de8106d7dc3f5684e01c05439" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478712,"asset_id":31045297,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045297"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045297"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045297; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045297]").text(description); $(".js-view-count[data-work-id=31045297]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045297; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045297']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045297, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "ee358b3de8106d7dc3f5684e01c05439" } } $('.js-work-strip[data-work-id=31045297]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045297,"title":"Clathrin-independent trafficking of AMPA receptors","translated_title":"","metadata":{"abstract":"Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.","publication_date":{"day":25,"month":1,"year":2015,"errors":{}},"publication_name":"The Journal of neuroscience : the official journal of the Society for Neuroscience"},"translated_abstract":"Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.","internal_url":"https://www.academia.edu/31045297/Clathrin_independent_trafficking_of_AMPA_receptors","translated_internal_url":"","created_at":"2017-01-23T03:27:07.929-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":28533068,"work_id":31045297,"tagging_user_id":1844143,"tagged_user_id":59323581,"co_author_invite_id":null,"email":"j***r@bristol.ac.uk","display_order":4194304,"name":"Jack Mellor","title":"Clathrin-independent trafficking of AMPA receptors"},{"id":28533069,"work_id":31045297,"tagging_user_id":1844143,"tagged_user_id":null,"co_author_invite_id":5777376,"email":"a***g@bristol.ac.uk","display_order":6291456,"name":"Oleg Glebov","title":"Clathrin-independent trafficking of AMPA receptors"}],"downloadable_attachments":[{"id":51478712,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478712/thumbnails/1.jpg","file_name":"4830.full.pdf","download_url":"https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Clathrin_independent_trafficking_of_AMPA.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478712/4830.full-libre.pdf?1485171118=\u0026response-content-disposition=attachment%3B+filename%3DClathrin_independent_trafficking_of_AMPA.pdf\u0026Expires=1732417380\u0026Signature=Q7uz5Du3WPgEmGbNGAHp6D0PmTryHEATOv5yaDJV0HGErEGvNzDIG-Y~fJqHTSv5jihlZaLjggmbVneEFJ2QS2vuZEVEbBOiL~tS0vpFZj5mehk~-ms6VwXLuUkCQkeUvg0Vyq9WuHo10FN6Z4l5XK3nqct~tEPvSkklfOfxZcnhLa9Oqx-qGhiaA4vxlMmnCF9MMhDg3fbwFT~ni4dTZ4p-SHK2ZSkXPDbhAqNADHrmu9TWhWk5DykuBidjemCpTxFUATHJMvdQjta-7RWK11l3ctTjkARrijsIZxBxsfoJ0h4FKR6MYDxkw66yf7fdLi388ihYqp841AmCmVbU9w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"slug":"Clathrin_independent_trafficking_of_AMPA_receptors","translated_slug":"","page_count":7,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[{"id":51478712,"title":"","file_type":"pdf","scribd_thumbnail_url":"https://attachments.academia-assets.com/51478712/thumbnails/1.jpg","file_name":"4830.full.pdf","download_url":"https://www.academia.edu/attachments/51478712/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&","bulk_download_file_name":"Clathrin_independent_trafficking_of_AMPA.pdf","bulk_download_url":"https://d1wqtxts1xzle7.cloudfront.net/51478712/4830.full-libre.pdf?1485171118=\u0026response-content-disposition=attachment%3B+filename%3DClathrin_independent_trafficking_of_AMPA.pdf\u0026Expires=1732417380\u0026Signature=Q7uz5Du3WPgEmGbNGAHp6D0PmTryHEATOv5yaDJV0HGErEGvNzDIG-Y~fJqHTSv5jihlZaLjggmbVneEFJ2QS2vuZEVEbBOiL~tS0vpFZj5mehk~-ms6VwXLuUkCQkeUvg0Vyq9WuHo10FN6Z4l5XK3nqct~tEPvSkklfOfxZcnhLa9Oqx-qGhiaA4vxlMmnCF9MMhDg3fbwFT~ni4dTZ4p-SHK2ZSkXPDbhAqNADHrmu9TWhWk5DykuBidjemCpTxFUATHJMvdQjta-7RWK11l3ctTjkARrijsIZxBxsfoJ0h4FKR6MYDxkw66yf7fdLi388ihYqp841AmCmVbU9w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience"},{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus"},{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":111545,"name":"Male","url":"https://www.academia.edu/Documents/in/Male"},{"id":193974,"name":"Neurons","url":"https://www.academia.edu/Documents/in/Neurons"},{"id":362533,"name":"Hydrazones","url":"https://www.academia.edu/Documents/in/Hydrazones"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":1457054,"name":"Protein Transport","url":"https://www.academia.edu/Documents/in/Protein_Transport"},{"id":1549061,"name":"Clathrin","url":"https://www.academia.edu/Documents/in/Clathrin"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045296"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_"><img alt="Research paper thumbnail of [Molecular mechanism of tolerance for vasodilator nitrates]" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_">[Molecular mechanism of tolerance for vasodilator nitrates]</a></div><div class="wp-workCard_item"><span>Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045296"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045296"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045296; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045296]").text(description); $(".js-view-count[data-work-id=31045296]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045296; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045296']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045296, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045296]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045296,"title":"[Molecular mechanism of tolerance for vasodilator nitrates]","translated_title":"","metadata":{"publication_name":"Revista de medicină internă, neurologe, psihiatrie, neurochirurgie, dermato-venerologie. Medicină internă"},"translated_abstract":null,"internal_url":"https://www.academia.edu/31045296/_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_","translated_internal_url":"","created_at":"2017-01-23T03:27:07.162-08:00","preview_url":null,"current_user_can_edit":null,"current_user_is_owner":null,"owner_id":1844143,"coauthors_can_edit":true,"document_type":"paper","co_author_tags":[{"id":28533071,"work_id":31045296,"tagging_user_id":1844143,"tagged_user_id":32831476,"co_author_invite_id":null,"email":"s***u@gmail.com","affiliation":"University of Bucharest","display_order":0,"name":"Stefan Constantinescu","title":"[Molecular mechanism of tolerance for vasodilator nitrates]"},{"id":28533072,"work_id":31045296,"tagging_user_id":1844143,"tagged_user_id":37893974,"co_author_invite_id":null,"email":"m***u@yahoo.com","display_order":4194304,"name":"Mihail Hinescu","title":"[Molecular mechanism of tolerance for vasodilator nitrates]"}],"downloadable_attachments":[],"slug":"_Molecular_mechanism_of_tolerance_for_vasodilator_nitrates_","translated_slug":"","page_count":null,"language":"en","content_type":"Work","owner":{"id":1844143,"first_name":"Cezar","middle_initials":null,"last_name":"Tigaret","page_name":"CezarTigaret","domain_name":"cardiff","created_at":"2012-05-29T01:58:24.217-07:00","display_name":"Cezar Tigaret","url":"https://cardiff.academia.edu/CezarTigaret"},"attachments":[],"research_interests":[{"id":99234,"name":"Animals","url":"https://www.academia.edu/Documents/in/Animals"},{"id":99271,"name":"Calcium channels","url":"https://www.academia.edu/Documents/in/Calcium_channels"},{"id":122402,"name":"Nitrates","url":"https://www.academia.edu/Documents/in/Nitrates"},{"id":419370,"name":"Swine","url":"https://www.academia.edu/Documents/in/Swine"},{"id":1592853,"name":"Drug Tolerance","url":"https://www.academia.edu/Documents/in/Drug_Tolerance"}],"urls":[]}, dispatcherData: dispatcherData }); $(this).data('initialized', true); } }); $a.trackClickSource(".js-work-strip-work-link", "profile_work_strip") }); </script> <div class="js-work-strip profile--work_container" data-work-id="31045295"><div class="profile--work_thumbnail hidden-xs"><a class="js-work-strip-work-link" data-click-track="profile-work-strip-thumbnail" href="https://www.academia.edu/31045295/Decreased_alpha_1_adrenergic_receptors_after_experimental_brain_injury"><img alt="Research paper thumbnail of Decreased alpha 1-adrenergic receptors after experimental brain injury" class="work-thumbnail" src="https://a.academia-assets.com/images/blank-paper.jpg" /></a></div><div class="wp-workCard wp-workCard_itemContainer"><div class="wp-workCard_item wp-workCard--title"><a class="js-work-strip-work-link text-gray-darker" data-click-track="profile-work-strip-title" href="https://www.academia.edu/31045295/Decreased_alpha_1_adrenergic_receptors_after_experimental_brain_injury">Decreased alpha 1-adrenergic receptors after experimental brain injury</a></div><div class="wp-workCard_item"><span>Journal of neurotrauma</span><span>, 1992</span></div><div class="wp-workCard_item"><span class="js-work-more-abstract-truncated">The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, ...</span><a class="js-work-more-abstract" data-broccoli-component="work_strip.more_abstract" data-click-track="profile-work-strip-more-abstract" href="javascript:;"><span> more </span><span><i class="fa fa-caret-down"></i></span></a><span class="js-work-more-abstract-untruncated hidden">The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p &lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of le...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045295"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045295"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045295; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045295]").text(description); $(".js-view-count[data-work-id=31045295]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045295; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045295']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045295, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (false){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "-1" } } $('.js-work-strip[data-work-id=31045295]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045295,"title":"Decreased alpha 1-adrenergic receptors after experimental brain injury","translated_title":"","metadata":{"abstract":"The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p \u0026lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. Conversely, at 24 h posttrauma, specific binding to membranes of le...","publication_date":{"day":null,"month":null,"year":1992,"errors":{}},"publication_name":"Journal of neurotrauma"},"translated_abstract":"The magnitude of neuronal damage in central nervous system (CNS) injury may be related, in part, to alterations in the balance between excitatory and inhibitory neurotransmitters. Previous studies have implicated a role of central inhibitory noradrenergic mechanisms in the pathophysiologic sequelae of traumatic brain injury. In the present study, we examined alpha 1-adrenergic receptor binding after parasaggital lateral fluid percussion (FP) brain injury of moderate severity (2.3 atm) in the rat. At 30 min following injury, the specific binding of [3H]prazosin to membranes isolated from left cortex (injury site) was reduced by 37% in brain-injured animals when compared to sham-operated noninjured animals (p \u0026lt; 0.05). However, there were no significant differences in [3H]prazosin binding to membranes of either contralateral (right) cortex or left and right hippocampi between brain-injured and sham-operated animals. 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In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. Furthermore, the NR1 N598R mutation does not affect expression levels of NM...</span></div><div class="wp-workCard_item wp-workCard--actions"><span class="work-strip-bookmark-button-container"></span><a id="790ec9fdd336c118de52ddfbc22a4a05" class="wp-workCard--action" rel="nofollow" data-click-track="profile-work-strip-download" data-download="{"attachment_id":51478715,"asset_id":31045294,"asset_type":"Work","button_location":"profile"}" href="https://www.academia.edu/attachments/51478715/download_file?st=MTczMjQxMzc4MCw4LjIyMi4yMDguMTQ2&s=profile"><span><i class="fa fa-arrow-down"></i></span><span>Download</span></a><span class="wp-workCard--action visible-if-viewed-by-owner inline-block" style="display: none;"><span class="js-profile-work-strip-edit-button-wrapper profile-work-strip-edit-button-wrapper" data-work-id="31045294"><a class="js-profile-work-strip-edit-button" tabindex="0"><span><i class="fa fa-pencil"></i></span><span>Edit</span></a></span></span><span id="work-strip-rankings-button-container"></span></div><div class="wp-workCard_item wp-workCard--stats"><span><span><span class="js-view-count view-count u-mr2x" data-work-id="31045294"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 31045294; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=31045294]").text(description); $(".js-view-count[data-work-id=31045294]").attr('title', description).tooltip(); }); });</script></span></span><span><span class="percentile-widget hidden"><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 31045294; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-work-strip[data-work-id='31045294']"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></span><span><script>$(function() { new Works.PaperRankView({ workId: 31045294, container: "", }); });</script></span></div><div id="work-strip-premium-row-container"></div></div></div><script> require.config({ waitSeconds: 90 })(["https://a.academia-assets.com/assets/wow_profile-f77ea15d77ce96025a6048a514272ad8becbad23c641fc2b3bd6e24ca6ff1932.js","https://a.academia-assets.com/assets/work_edit-ad038b8c047c1a8d4fa01b402d530ff93c45fee2137a149a4a5398bc8ad67560.js"], function() { // from javascript_helper.rb var dispatcherData = {} if (true){ window.WowProfile.dispatcher = window.WowProfile.dispatcher || _.clone(Backbone.Events); dispatcherData = { dispatcher: window.WowProfile.dispatcher, downloadLinkId: "790ec9fdd336c118de52ddfbc22a4a05" } } $('.js-work-strip[data-work-id=31045294]').each(function() { if (!$(this).data('initialized')) { new WowProfile.WorkStripView({ el: this, workJSON: {"id":31045294,"title":"Absence of Whisker-related pattern formation in mice with NMDA receptors lacking coincidence detection properties and calcium signaling","translated_title":"","metadata":{"abstract":"Precise refinement of synaptic connectivity is the result of activity-dependent mechanisms in which coincidence-dependent calcium signaling by NMDA receptors (NMDARs) under control of the voltage-dependent Mg2+ block might play a special role. In the developing rodent trigeminal system, the pattern of synaptic connections between whisker-specific inputs and their target cells in the brainstem is refined to form functionally and morphologically distinct units (barrelettes). To test the role of NMDA receptor signaling in this process, we introduced the N598R mutation into the native NR1 gene. This leads to the expression of functional NMDARs that are Mg2+ insensitive and Ca2+ impermeable. Newborn mice expressing exclusively NR1 N598R-containing NMDARs do not show any whisker-related patterning in the brainstem, whereas the topographic projection of trigeminal afferents and gross brain morphology appear normal. 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