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The ability of a presynaptic terminal to reuse its vesicular content is thought to be a signature of synaptic... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_24186466" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Background: In terms of vesicular recycling, synaptic efficiency is a key determinant of the fidelity of synaptic transmission. The ability of a presynaptic terminal to reuse its vesicular content is thought to be a signature of synaptic maturity and this process depends on the activity of several proteins that govern exo/endocytosis. Upon stimulation, individual terminals in networks of cultured cerebellar granule neurons exhibit heterogeneous exocytic responses, which reflect the distinct states of maturity and plasticity intrinsic to individual synaptic terminals. This dynamic scenario serves as the substrate for processes such as scaling, plasticity and synaptic weight redistribution. Presynaptic strength has been associated with the activity of several types of proteins, including the scaffolding proteins that form the active zone cytomatrix and the proteins involved in presynaptic exocytosis.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24186466" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="945ba19d8c0b7039caad3192988ead0f" rel="nofollow" data-download="{"attachment_id":44520581,"asset_id":24186466,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520581/download_file?st=MTczNDEzMTI3MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24186466">+1</span><div class="hidden js-additional-users-24186466"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24186466'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24186466').html(); 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As there are distinct endocytotic pathways that each differ in their efficiency... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_24186684" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture increased the proportion of synaptic boutons that were capable of an intense release response, whereas the chronic blockage of synaptic activity diminished the capacity of boutons to release dye.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24186684" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="1ec48163c49c2bc79b73b06f9502eb20" rel="nofollow" data-download="{"attachment_id":44520595,"asset_id":24186684,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520595/download_file?st=MTczNDEzMTI3MCw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24186684">+1</span><div class="hidden js-additional-users-24186684"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24186684'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24186684').html(); 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As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture increased the proportion of synaptic boutons that were capable of an intense release response, whereas the chronic blockage of synaptic activity diminished the capacity of boutons to release dye.","publication":null,"publication_with_fallback":null,"downloadable_attachments":[{"id":44520595,"asset_id":24186684,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520595/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520595/Bartolome-Martin_ety_al_JCS_2012_def_full-libre.pdf?1460079953=\u0026response-content-disposition=attachment%3B+filename%3DEfficient_synaptic_vesicle_recycling_aft.pdf\u0026Expires=1733443159\u0026Signature=FzRNb20f1aE6SO3rmc1ZRTP1rCq2JqyaWTC1aIhu2TBupjws66jFjm61LdkjgXVW225jd8w1n86zGlL2teGJkZtCnOu4dLC69gQYcVgUlEjTikKsZ0cDYZvJg~5oZl-kTa2NcuwAPmnkkty~newqvwJZ8L~7dtJbYkJ0QFcoCVq3LxcP12bL5UVQhT9NqyjSeaC37JaY5hzVpS5vQ2Tz6~mkfU1zF2TcGwoCFx~n-EV0h6ZpQPO-bqMFymT3St2JQWWrjq6KiUFEQOmFF6BrnLcMUTMP5zamwMg7ja~Y7~b6gQ68aouZy-PLZnXlxAthfYgINtRiDL8N5oFFLuUn7A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520595/download_file?st=MTczNDEzMTI3MCw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520595/mini_magick20190214-13785-1jj5y9r.png?1550166758"}],"downloadable_attachments_with_full_thumbnails":[{"id":44520595,"asset_id":24186684,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520595/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520595/Bartolome-Martin_ety_al_JCS_2012_def_full-libre.pdf?1460079953=\u0026response-content-disposition=attachment%3B+filename%3DEfficient_synaptic_vesicle_recycling_aft.pdf\u0026Expires=1733443159\u0026Signature=FzRNb20f1aE6SO3rmc1ZRTP1rCq2JqyaWTC1aIhu2TBupjws66jFjm61LdkjgXVW225jd8w1n86zGlL2teGJkZtCnOu4dLC69gQYcVgUlEjTikKsZ0cDYZvJg~5oZl-kTa2NcuwAPmnkkty~newqvwJZ8L~7dtJbYkJ0QFcoCVq3LxcP12bL5UVQhT9NqyjSeaC37JaY5hzVpS5vQ2Tz6~mkfU1zF2TcGwoCFx~n-EV0h6ZpQPO-bqMFymT3St2JQWWrjq6KiUFEQOmFF6BrnLcMUTMP5zamwMg7ja~Y7~b6gQ68aouZy-PLZnXlxAthfYgINtRiDL8N5oFFLuUn7A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520595/download_file?st=MTczNDEzMTI3MCw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520595/mini_magick20190214-13785-1jj5y9r.png?1550166758"}],"has_pdf":true,"has_fulltext":true,"page_count":19,"ordered_authors":[{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"},{"id":38011380,"first_name":"Magdalena","last_name":"Torres","domain_name":"ucm-sk","page_name":"MagdalenaTorres","display_name":"Magdalena Torres","profile_url":"https://ucm-sk.academia.edu/MagdalenaTorres","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":90156,"name":"Endocytosis","url":"https://www.academia.edu/Documents/in/Endocytosis","nofollow":false},{"id":182193,"name":"Synaptic Vesicle Recycling","url":"https://www.academia.edu/Documents/in/Synaptic_Vesicle_Recycling","nofollow":false},{"id":1654784,"name":"Cerebellar Granule Neuron","url":"https://www.academia.edu/Documents/in/Cerebellar_Granule_Neuron","nofollow":false}],"publication_year":null,"publication_year_with_fallback":null,"paper_rank":null,"all_time_views":17,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_24186896 coauthored" data-work_id="24186896" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/24186896/The_Regulation_of_Synaptic_Vesicle_Recycling_by_cGMP_Dependent_Protein_Kinase_Type_II_in_Cerebellar_Granule_Cells_under_Strong_and_Sustained_Stimulation">The Regulation of Synaptic Vesicle Recycling by cGMP- Dependent Protein Kinase Type II in Cerebellar Granule Cells under Strong and Sustained Stimulation</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">From the early periods of neurogenesis and migration, up until synaptogenesis, both nitric oxide (NO) and its downstream messenger, cGMP, are thought to influence the development of neurons. The NO/cGMP/cGMP-dependent protein kinase (cGK)... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_24186896" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">From the early periods of neurogenesis and migration, up until synaptogenesis, both nitric oxide (NO) and its downstream messenger, cGMP, are thought to influence the development of neurons. The NO/cGMP/cGMP-dependent protein kinase (cGK) pathway regulates the clustering and recruitment of synaptic proteins and vesicles to the synapse, adjusting the exoendocytic cycle to the intensity of activity and accelerating endocytosis following large-scale exocytosis. Here, we show that blockage of the N-methyl-D-aspartate receptor impairs the cycling of synaptic vesicles in a subset of boutons on cerebellar granule cells, an effect that was reversed by increasing cGMP. Furthermore, we demonstrate that presynaptic cGK type II (cGKII) plays a major role in this process. Using the FM1-43 dye to track vesicle recycling, we found that knockdown of cGKII and/or the application of a cGK inhibitor reduced the efficiency of synaptic vesicle recycling to a similar extent. Likewise, in cerebellar granule cells transfected with vGlut1-pHluorin to follow the exoendocytotic cycle, application of a cGK inhibitor slowed vesicle endocytosis when exocytosis was accelerated through strong and sustained stimulation. Additionally, ultrastructural analysis showed that cGKII knockdown or inhibition favored the formation of endosomal-like structures after strong and sustained stimulation. We conclude that cGKII controls the homeostatic balance of vesicle exocytosis and endocytosis in synaptic boutons of rat cerebellar granule cells.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24186896" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="259863f2be986b117f77ece0e64501bd" rel="nofollow" data-download="{"attachment_id":44520659,"asset_id":24186896,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520659/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="46651603" href="https://independent.academia.edu/AndreaColladoAlsina">Andrea Collado-Alsina</a><script data-card-contents-for-user="46651603" type="text/json">{"id":46651603,"first_name":"Andrea","last_name":"Collado-Alsina","domain_name":"independent","page_name":"AndreaColladoAlsina","display_name":"Andrea Collado-Alsina","profile_url":"https://independent.academia.edu/AndreaColladoAlsina","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24186896">+2</span><div class="hidden js-additional-users-24186896"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24186896'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24186896').html(); 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The NO/cGMP/cGMP-dependent protein kinase (cGK) pathway regulates the clustering and recruitment of synaptic proteins and vesicles to the synapse, adjusting the exoendocytic cycle to the intensity of activity and accelerating endocytosis following large-scale exocytosis. Here, we show that blockage of the N-methyl-D-aspartate receptor impairs the cycling of synaptic vesicles in a subset of boutons on cerebellar granule cells, an effect that was reversed by increasing cGMP. Furthermore, we demonstrate that presynaptic cGK type II (cGKII) plays a major role in this process. Using the FM1-43 dye to track vesicle recycling, we found that knockdown of cGKII and/or the application of a cGK inhibitor reduced the efficiency of synaptic vesicle recycling to a similar extent. Likewise, in cerebellar granule cells transfected with vGlut1-pHluorin to follow the exoendocytotic cycle, application of a cGK inhibitor slowed vesicle endocytosis when exocytosis was accelerated through strong and sustained stimulation. Additionally, ultrastructural analysis showed that cGKII knockdown or inhibition favored the formation of endosomal-like structures after strong and sustained stimulation. We conclude that cGKII controls the homeostatic balance of vesicle exocytosis and endocytosis in synaptic boutons of rat cerebellar granule cells.","publication":null,"publication_with_fallback":"The Journal of Neuroscience","downloadable_attachments":[{"id":44520659,"asset_id":24186896,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520659/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520659/Collado-Alsina_2014_The_Regulation_of_Synaptic_Vesicle_Recycling_-libre.pdf?1460080127=\u0026response-content-disposition=attachment%3B+filename%3DThe_Regulation_of_Synaptic_Vesicle_Recyc.pdf\u0026Expires=1734134870\u0026Signature=ISKMtc0WaPlq328WcRm550D0OotwYiz~I-kjMocWl9dVFfQbVWdkXn-1fxNUitznQOKNfJFNkevXgawh-1iaipNJ5NgLf5ngE2oFR51f~MIy6nRVjEsZAxGDFycSaFNcUlN05EowayCmhFJlyyJNWIfJ9FyYUh2mPa04KHRW0lXkjoHwFJEPl-hwoHq9D4yWr0BjxvHazejhIYB~bi6LvCy9psZ5Mw9zjRYFEQUSyQAlpvGf0cSZApqz7E-DGi-bdze1JpDqX~HAs97WV31dVqD1UAVanCJ98yw1txZVIcU4nvhEctiCCN4yKbabOrE5zg5L53EhglaUUkp62Wca1w__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520659/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520659/mini_magick20190214-13788-1olu027.png?1550166758"}],"downloadable_attachments_with_full_thumbnails":[{"id":44520659,"asset_id":24186896,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520659/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520659/Collado-Alsina_2014_The_Regulation_of_Synaptic_Vesicle_Recycling_-libre.pdf?1460080127=\u0026response-content-disposition=attachment%3B+filename%3DThe_Regulation_of_Synaptic_Vesicle_Recyc.pdf\u0026Expires=1734134871\u0026Signature=FGuBjHCmt267BnJk1uUfODa7jEIYK-vfNEbI-uriBdAcIDPIP7OE42TJzWjanEnagjexy32NXgE0HiX~rLHpRhlGrHMwtpQyTvdfeG9EDabPpdAX7D2q-A2ZfM-jqH5u~-WeTSQeZUeDDfXWYQbF2ACOaolb2vZ65ZFy0embJ22BkkkZ4NNSBp7gfwKR8BaO-JHKR~2dTrde0QOhYDgwjwqQFXuFBwP-Hx~Lx0gQ3cynqn5-wAMySKTiCZA-JyEK59wuJtf8FUzsodCF4gPL09F3a5uRxoxBDb4VmnTvPYXPKtrsDEaONnGo7YgVkxYvtVcZs5s4GsiT3sfFeTbt3A__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520659/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520659/mini_magick20190214-13788-1olu027.png?1550166758"}],"has_pdf":true,"has_fulltext":true,"page_count":12,"ordered_authors":[{"id":46651603,"first_name":"Andrea","last_name":"Collado-Alsina","domain_name":"independent","page_name":"AndreaColladoAlsina","display_name":"Andrea Collado-Alsina","profile_url":"https://independent.academia.edu/AndreaColladoAlsina","photo":"/images/s65_no_pic.png"},{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"},{"id":38011380,"first_name":"Magdalena","last_name":"Torres","domain_name":"ucm-sk","page_name":"MagdalenaTorres","display_name":"Magdalena Torres","profile_url":"https://ucm-sk.academia.edu/MagdalenaTorres","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":182193,"name":"Synaptic Vesicle Recycling","url":"https://www.academia.edu/Documents/in/Synaptic_Vesicle_Recycling","nofollow":false},{"id":353872,"name":"Cgmp","url":"https://www.academia.edu/Documents/in/Cgmp","nofollow":false},{"id":1242330,"name":"cGMP-regulated protein kinase","url":"https://www.academia.edu/Documents/in/cGMP-regulated_protein_kinase","nofollow":false},{"id":1654784,"name":"Cerebellar Granule Neuron","url":"https://www.academia.edu/Documents/in/Cerebellar_Granule_Neuron","nofollow":false}],"publication_year":null,"publication_year_with_fallback":2014,"paper_rank":null,"all_time_views":17,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_24186962 coauthored" data-work_id="24186962" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/24186962/Daidzein_has_neuroprotective_effects_through_ligand_binding_independent_PPARc_activation">Daidzein has neuroprotective effects through ligand-binding-independent PPARc activation</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_24186962" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: <a href="http://www.elsevier.com/copyright" rel="nofollow">http://www.elsevier.com/copyright</a> a b s t r a c t Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-c (PPARc), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARc. Our results show that daidzein (0.05–5 lM) decreases cell death induced by exposure to oxygen–glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARc antagonist T0070907 (1 lM). In addition, this phytoestrogen activated PPARc in neuronal cultures, as shown by an increase in PPARc transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARc competitive binding assay. Conversely, daidzein increased PPARc nuclear protein levels and decreased cytosolic ones, suggesting nuclear trans-location. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARc activity not mediated by direct binding to the receptor ligand-binding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24186962" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="9d14017042e8dc1fd7b22b052f607440" rel="nofollow" data-download="{"attachment_id":44520716,"asset_id":24186962,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520716/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24186962">+2</span><div class="hidden js-additional-users-24186962"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JPradillo">J. Pradillo</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24186962'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24186962').html(); } } new HoverPopover(popoverSettings); })();</script></li><li class="js-paper-rank-work_24186962 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="24186962"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 24186962, container: ".js-paper-rank-work_24186962", }); });</script></li><li class="js-percentile-work_24186962 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 24186962; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_24186962"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_24186962 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="24186962"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 24186962; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=24186962]").text(description); $(".js-view-count-work_24186962").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_24186962").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="24186962"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">4</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="37851" href="https://www.academia.edu/Documents/in/Neuroprotection">Neuroprotection</a>, <script data-card-contents-for-ri="37851" type="text/json">{"id":37851,"name":"Neuroprotection","url":"https://www.academia.edu/Documents/in/Neuroprotection","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="61234" href="https://www.academia.edu/Documents/in/Stroke">Stroke</a>, <script data-card-contents-for-ri="61234" type="text/json">{"id":61234,"name":"Stroke","url":"https://www.academia.edu/Documents/in/Stroke","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="1338247" href="https://www.academia.edu/Documents/in/PPARgamma">PPARgamma</a>, <script data-card-contents-for-ri="1338247" type="text/json">{"id":1338247,"name":"PPARgamma","url":"https://www.academia.edu/Documents/in/PPARgamma","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="2440183" href="https://www.academia.edu/Documents/in/Daidzein">Daidzein</a><script data-card-contents-for-ri="2440183" type="text/json">{"id":2440183,"name":"Daidzein","url":"https://www.academia.edu/Documents/in/Daidzein","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=24186962]'), work: {"id":24186962,"title":"Daidzein has neuroprotective effects through ligand-binding-independent PPARc activation","created_at":"2016-04-07T17:27:03.869-07:00","owner_id":43706937,"url":"https://www.academia.edu/24186962/Daidzein_has_neuroprotective_effects_through_ligand_binding_independent_PPARc_activation","slug":"Daidzein_has_neuroprotective_effects_through_ligand_binding_independent_PPARc_activation","dom_id":"work_24186962","summary":"This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright a b s t r a c t Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-c (PPARc), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARc. Our results show that daidzein (0.05–5 lM) decreases cell death induced by exposure to oxygen–glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARc antagonist T0070907 (1 lM). In addition, this phytoestrogen activated PPARc in neuronal cultures, as shown by an increase in PPARc transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARc competitive binding assay. Conversely, daidzein increased PPARc nuclear protein levels and decreased cytosolic ones, suggesting nuclear trans-location. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARc activity not mediated by direct binding to the receptor ligand-binding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.","publication":null,"publication_with_fallback":null,"downloadable_attachments":[{"id":44520716,"asset_id":24186962,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520716/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520716/Hurtado_et_al_Phytostrogens_Neurochem_international_2012-libre.pdf?1460080188=\u0026response-content-disposition=attachment%3B+filename%3DDaidzein_has_neuroprotective_effects_thr.pdf\u0026Expires=1734134871\u0026Signature=g0Fm7KS0aDS6~hl2bf2W1nXUikbqUgx9H9Mf7-FDVT3pg7MBWmNOdjl8yA1vRYqgKdbRGTDcRyz81e0c8xHhJthZfGNfk57LUp~U9Lao-CEehrvuGD9V5yRsUezk94il-pa3KYWRgsgUmFl4RamUkmF-0yklT9iJ7vC3egPKyKDcbtqcVCM2PUqVwpngwKLL4Q1kmfzy4WsWD-Y-ULttIAZMtEDXc~01RvMBp~fUMHV~-jIR~TqboO7jek-zCpsgRdYcuhDCQP-oAbERzVmm29Y1aOmdpNzBvAJ3VoIjInLeSnvOYux2~7dKvBsJPvmK8TuBNvHkJRkAEVhZXAZPug__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520716/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520716/mini_magick20190214-6063-vgk2cv.png?1550166765"}],"downloadable_attachments_with_full_thumbnails":[{"id":44520716,"asset_id":24186962,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520716/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520716/Hurtado_et_al_Phytostrogens_Neurochem_international_2012-libre.pdf?1460080188=\u0026response-content-disposition=attachment%3B+filename%3DDaidzein_has_neuroprotective_effects_thr.pdf\u0026Expires=1734134871\u0026Signature=g0Fm7KS0aDS6~hl2bf2W1nXUikbqUgx9H9Mf7-FDVT3pg7MBWmNOdjl8yA1vRYqgKdbRGTDcRyz81e0c8xHhJthZfGNfk57LUp~U9Lao-CEehrvuGD9V5yRsUezk94il-pa3KYWRgsgUmFl4RamUkmF-0yklT9iJ7vC3egPKyKDcbtqcVCM2PUqVwpngwKLL4Q1kmfzy4WsWD-Y-ULttIAZMtEDXc~01RvMBp~fUMHV~-jIR~TqboO7jek-zCpsgRdYcuhDCQP-oAbERzVmm29Y1aOmdpNzBvAJ3VoIjInLeSnvOYux2~7dKvBsJPvmK8TuBNvHkJRkAEVhZXAZPug__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520716/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520716/mini_magick20190214-6063-vgk2cv.png?1550166765"}],"has_pdf":true,"has_fulltext":true,"page_count":10,"ordered_authors":[{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"},{"id":38011380,"first_name":"Magdalena","last_name":"Torres","domain_name":"ucm-sk","page_name":"MagdalenaTorres","display_name":"Magdalena Torres","profile_url":"https://ucm-sk.academia.edu/MagdalenaTorres","photo":"/images/s65_no_pic.png"},{"id":38112353,"first_name":"J.","last_name":"Pradillo","domain_name":"independent","page_name":"JPradillo","display_name":"J. 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The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1a protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24187035" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="4090e5cbfe70572b4a61ba46ddc82275" rel="nofollow" data-download="{"attachment_id":44520739,"asset_id":24187035,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520739/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24187035">+1</span><div class="hidden js-additional-users-24187035"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24187035'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24187035').html(); 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The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchange Protein directly Activated by cAMP (Epac). Furthermore, Epac activation accelerated awakening of already silent boutons. Electron microscopy revealed that silencing was associated with synaptic vesicle (SV) redistribution within the nerve terminal, which diminished the number of vesicles close to the active zone of the plasma membrane. Finally, by combining functional and immunocytochemical approaches, we observed a strong correlation between the release capacity of the nerve terminals and RIM1a protein content, but not that of Munc13-1 protein. These results suggest that prolonged stimulation of cannabinoid receptors can transiently silence glutamatergic nerve terminals.","publication":null,"publication_with_fallback":null,"downloadable_attachments":[{"id":44520739,"asset_id":24187035,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520739/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520739/Ramirez-Franco_et_al_Cannabinoid_Type_1_Receptors_Transiently_Silence__PLoS_one_2014-libre.pdf?1460080226=\u0026response-content-disposition=attachment%3B+filename%3DCannabinoid_Type_1_Receptors_Transiently.pdf\u0026Expires=1734134871\u0026Signature=KzXe90Di1TPFN8t8LHv9nmv~zrL0LM5AMMvK-Ohjh6T4GcujEWJ0gEep4Ixdg3ulVONqr1Br35kf1rt08JIs2Qg5N6xOiNRgS-Zij-6nXKEhRwIFLdbFLzsEXF9nnQ7jaDiAokCTWnANUYnAcqaqeX0bjm82~xH~IemUanzGNHvGSpq4JEklpN4Ykp2P1pDRE1GA~ygM0UGQduOpiZ8kFpga5rU9esoJlPNchGiHJA3M0p18ZN4t9ZT0XtEB2RqHF8YUL49soC8F-TwpgtfVHuQ34LvuqYXEJg-~-VKkh34SclKhVrlZAaPkrtJ~tDh6VU~1oIyK4POWe5ytYwBtQQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520739/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520739/mini_magick20220702-31279-12uqhj2.png?1656746220"}],"downloadable_attachments_with_full_thumbnails":[{"id":44520739,"asset_id":24187035,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/44520739/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/44520739/Ramirez-Franco_et_al_Cannabinoid_Type_1_Receptors_Transiently_Silence__PLoS_one_2014-libre.pdf?1460080226=\u0026response-content-disposition=attachment%3B+filename%3DCannabinoid_Type_1_Receptors_Transiently.pdf\u0026Expires=1734134871\u0026Signature=KzXe90Di1TPFN8t8LHv9nmv~zrL0LM5AMMvK-Ohjh6T4GcujEWJ0gEep4Ixdg3ulVONqr1Br35kf1rt08JIs2Qg5N6xOiNRgS-Zij-6nXKEhRwIFLdbFLzsEXF9nnQ7jaDiAokCTWnANUYnAcqaqeX0bjm82~xH~IemUanzGNHvGSpq4JEklpN4Ykp2P1pDRE1GA~ygM0UGQduOpiZ8kFpga5rU9esoJlPNchGiHJA3M0p18ZN4t9ZT0XtEB2RqHF8YUL49soC8F-TwpgtfVHuQ34LvuqYXEJg-~-VKkh34SclKhVrlZAaPkrtJ~tDh6VU~1oIyK4POWe5ytYwBtQQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/44520739/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/44520739/mini_magick20220702-31279-12uqhj2.png?1656746220"}],"has_pdf":true,"has_fulltext":true,"page_count":15,"ordered_authors":[{"id":43706937,"first_name":"JOSE 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Synapses","url":"https://www.academia.edu/Documents/in/Silent_Synapses","nofollow":false}],"publication_year":null,"publication_year_with_fallback":null,"paper_rank":null,"all_time_views":10,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_24187073 coauthored" data-work_id="24187073" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/24187073/Cross_talk_between_metabotropic_glutamate_receptor_7_and_beta_adrenergic_receptor_signaling_at_cerebrocortical_nerve_terminals">Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest">Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals, Neuropharmacology (2015),</div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24187073" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="3d0ea9bb0690ab3bb9ad09faa547f24d" rel="nofollow" data-download="{"attachment_id":44520791,"asset_id":24187073,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button 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data-has-card-for-ri="357638" href="https://www.academia.edu/Documents/in/Beta-Adrenergic_Receptors">Beta-Adrenergic Receptors</a>, <script data-card-contents-for-ri="357638" type="text/json">{"id":357638,"name":"Beta-Adrenergic Receptors","url":"https://www.academia.edu/Documents/in/Beta-Adrenergic_Receptors","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="561971" href="https://www.academia.edu/Documents/in/SYNAPTOSOMES">SYNAPTOSOMES</a>, <script data-card-contents-for-ri="561971" type="text/json">{"id":561971,"name":"SYNAPTOSOMES","url":"https://www.academia.edu/Documents/in/SYNAPTOSOMES","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="2440189" href="https://www.academia.edu/Documents/in/Glutamate_release">Glutamate release</a><script data-card-contents-for-ri="2440189" type="text/json">{"id":2440189,"name":"Glutamate 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physiological responses of AMPA receptors can be modulated through the differential expression of their subunits and by modifying their number at the cell surface. Here we have studied the expression of AMPA receptor subunits... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_24187080" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">The physiological responses of AMPA receptors can be modulated through the differential expression of their subunits and by modifying their number at the cell surface. Here we have studied the expression of AMPA receptor subunits (GluR1–4) mRNAs in cerebellar granule cells grown in depolarizing (25 mM K +) medium, and we have evaluated the effect of decreasing the [K + ] in the culture medium for 24 h on both GluR1–4 expression (both mRNA and protein) and their presence at the plasma membrane. The expression of the four AMPAR subunits increases as the [K + ] decreases, although the increase in GluR2 and GluR3 was only observed in the cell soma but not in the dendrites. Calcium entry through L-type calcium channel and CaMKIV activation are responsible for the reduction in the expression of AMPA receptor subunits in cells cultured in depolarizing conditions. Indeed, prolonged reduction of extracellular [K + ] or blockage of L-type calcium channels enhanced both the surface insertion of the four AMPAR subunits and the AMPA response measured through intracellular calcium increase. These findings reveal a balanced increase in functional AMPA receptors at the surface of cells that can trigger strong increases in calcium in response to the persistent reduction of calcium entry.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/24187080" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="d3d1d4eb6fd9dca9ace0fae64bfb9acf" rel="nofollow" data-download="{"attachment_id":44520817,"asset_id":24187080,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/44520817/download_file?st=MTczNDEzMTI3MSw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-24187080">+2</span><div class="hidden js-additional-users-24187080"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JorgeRamirezFranco">Jorge Ramírez-Franco</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-24187080'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-24187080').html(); 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The ability of a presynaptic terminal to reuse its vesicular content is thought to be a signature of synaptic... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_25928714" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Background: In terms of vesicular recycling, synaptic efficiency is a key determinant of the fidelity of synaptic transmission. The ability of a presynaptic terminal to reuse its vesicular content is thought to be a signature of synaptic maturity and this process depends on the activity of several proteins that govern exo/endocytosis. Upon stimulation, individual terminals in networks of cultured cerebellar granule neurons exhibit heterogeneous exocytic responses, which reflect the distinct states of maturity and plasticity intrinsic to individual synaptic terminals. This dynamic scenario serves as the substrate for processes such as scaling, plasticity and synaptic weight redistribution. Presynaptic strength has been associated with the activity of several types of proteins, including the scaffolding proteins that form the active zone cytomatrix and the proteins involved in presynaptic exocytosis.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/25928714" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="581f55654e0fadd14b5af5188b2a2e5d" rel="nofollow" data-download="{"attachment_id":46286462,"asset_id":25928714,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/46286462/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="49637377" href="https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn">David Bartolomé-Martín</a><script data-card-contents-for-user="49637377" type="text/json">{"id":49637377,"first_name":"David","last_name":"Bartolomé-Martín","domain_name":"uam","page_name":"DavidBartoloméMartín","display_name":"David Bartolomé-Martín","profile_url":"https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-25928714">+4</span><div class="hidden js-additional-users-25928714"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm.academia.edu/JSanchezprieto">J. Sanchez-prieto</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JorgeRamirezFranco">Jorge Ramírez-Franco</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-25928714'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-25928714').html(); } } new HoverPopover(popoverSettings); })();</script></li><li class="js-paper-rank-work_25928714 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="25928714"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 25928714, container: ".js-paper-rank-work_25928714", }); });</script></li><li class="js-percentile-work_25928714 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 25928714; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_25928714"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_25928714 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="25928714"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 25928714; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=25928714]").text(description); $(".js-view-count-work_25928714").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_25928714").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="25928714"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">14</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="237" href="https://www.academia.edu/Documents/in/Cognitive_Science">Cognitive Science</a>, <script data-card-contents-for-ri="237" type="text/json">{"id":237,"name":"Cognitive Science","url":"https://www.academia.edu/Documents/in/Cognitive_Science","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="1185" href="https://www.academia.edu/Documents/in/Image_Processing">Image Processing</a>, <script data-card-contents-for-ri="1185" type="text/json">{"id":1185,"name":"Image Processing","url":"https://www.academia.edu/Documents/in/Image_Processing","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="12071" href="https://www.academia.edu/Documents/in/Immunohistochemistry">Immunohistochemistry</a>, <script data-card-contents-for-ri="12071" type="text/json">{"id":12071,"name":"Immunohistochemistry","url":"https://www.academia.edu/Documents/in/Immunohistochemistry","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="18529" href="https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents">Fluorescent Dyes and Reagents</a><script data-card-contents-for-ri="18529" type="text/json">{"id":18529,"name":"Fluorescent Dyes and Reagents","url":"https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=25928714]'), work: {"id":25928714,"title":"Studying synaptic efficiency by post-hoc immunolabelling","created_at":"2016-06-06T11:10:55.118-07:00","owner_id":49637377,"url":"https://www.academia.edu/25928714/Studying_synaptic_efficiency_by_post_hoc_immunolabelling","slug":"Studying_synaptic_efficiency_by_post_hoc_immunolabelling","dom_id":"work_25928714","summary":"Background: In terms of vesicular recycling, synaptic efficiency is a key determinant of the fidelity of synaptic transmission. The ability of a presynaptic terminal to reuse its vesicular content is thought to be a signature of synaptic maturity and this process depends on the activity of several proteins that govern exo/endocytosis. Upon stimulation, individual terminals in networks of cultured cerebellar granule neurons exhibit heterogeneous exocytic responses, which reflect the distinct states of maturity and plasticity intrinsic to individual synaptic terminals. This dynamic scenario serves as the substrate for processes such as scaling, plasticity and synaptic weight redistribution. Presynaptic strength has been associated with the activity of several types of proteins, including the scaffolding proteins that form the active zone cytomatrix and the proteins involved in presynaptic exocytosis.","publication":"BMC Neuroscience","publication_with_fallback":"BMC Neuroscience","downloadable_attachments":[{"id":46286462,"asset_id":25928714,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/46286462/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/46286462/Studying_synaptic_efficiency_by_post-hoc20160606-19389-uvwsi9-libre.pdf?1465237021=\u0026response-content-disposition=attachment%3B+filename%3DStudying_synaptic_efficiency_by_post_hoc.pdf\u0026Expires=1734134872\u0026Signature=D5GLmkuXaovruwYJ5mAZeQrkaFvahJs6dYDnpmc7yKh2xrNLeTWovuSNvyCGZDRUPdbRhrwebQ-TboAoGfFYLh6ArU36jq8dpVnnKpNBNJ1wmqGbSVWBlYKH-hFazuuy8dyJwlYd9n9pEFs~OKU1V7yQfGI065VJCf1uH06D-n2Zrg4VBIgoDzH1pixPy80skXuv1Nog-yeWp5~7mmvkAc7Lbbg56UYdYDE4KrfqVPWhTQ23btEWUH~BNTsc6RBshyUhmc3tO9R-WUD2iS-NRMdgnBTonJtco-EEPTSjWo2MviYpVGsAmVLnjORUE5RJHZ8RVNW7rxklOsHbkdoCWQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/46286462/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/46286462/mini_magick20190210-28571-18p9lxc.png?1549799903"}],"downloadable_attachments_with_full_thumbnails":[{"id":46286462,"asset_id":25928714,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/46286462/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/46286462/Studying_synaptic_efficiency_by_post-hoc20160606-19389-uvwsi9-libre.pdf?1465237021=\u0026response-content-disposition=attachment%3B+filename%3DStudying_synaptic_efficiency_by_post_hoc.pdf\u0026Expires=1734134872\u0026Signature=D5GLmkuXaovruwYJ5mAZeQrkaFvahJs6dYDnpmc7yKh2xrNLeTWovuSNvyCGZDRUPdbRhrwebQ-TboAoGfFYLh6ArU36jq8dpVnnKpNBNJ1wmqGbSVWBlYKH-hFazuuy8dyJwlYd9n9pEFs~OKU1V7yQfGI065VJCf1uH06D-n2Zrg4VBIgoDzH1pixPy80skXuv1Nog-yeWp5~7mmvkAc7Lbbg56UYdYDE4KrfqVPWhTQ23btEWUH~BNTsc6RBshyUhmc3tO9R-WUD2iS-NRMdgnBTonJtco-EEPTSjWo2MviYpVGsAmVLnjORUE5RJHZ8RVNW7rxklOsHbkdoCWQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/46286462/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/46286462/mini_magick20190210-28571-18p9lxc.png?1549799903"}],"has_pdf":true,"has_fulltext":true,"page_count":11,"ordered_authors":[{"id":49637377,"first_name":"David","last_name":"Bartolomé-Martín","domain_name":"uam","page_name":"DavidBartoloméMartín","display_name":"David Bartolomé-Martín","profile_url":"https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn","photo":"/images/s65_no_pic.png"},{"id":38118709,"first_name":"J.","last_name":"Sanchez-prieto","domain_name":"ucm","page_name":"JSanchezprieto","display_name":"J. 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As there are distinct endocytotic pathways that each differ in their efficiency... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_25928715" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture increased the proportion of synaptic boutons that were capable of an intense release response, whereas the chronic blockage of synaptic activity diminished the capacity of boutons to release dye. by either a weak or a strong loss of FM1-43. Endocytosis in both subsets of nerve terminals was sensitive to the dynamin inhibitor dynasore, which completely prevented dye unloading and dramatically diminished the number of synaptic vesicles. Decreasing the intensity of exocytosis increased the proportion of synaptic boutons that lose large amounts of dye and reduced the presence of endosome-like structures. Together, these findings demonstrate that efficient vesicle-recycling pathways coexist with those pathways that involve the formation of non-releasable endosomes in synaptic boutons, although in different proportions.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/25928715" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="ee2c562259a1ba4111ec992cace05b53" rel="nofollow" data-download="{"attachment_id":46286463,"asset_id":25928715,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/46286463/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="49637377" href="https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn">David Bartolomé-Martín</a><script data-card-contents-for-user="49637377" type="text/json">{"id":49637377,"first_name":"David","last_name":"Bartolomé-Martín","domain_name":"uam","page_name":"DavidBartoloméMartín","display_name":"David Bartolomé-Martín","profile_url":"https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn","photo":"/images/s65_no_pic.png"}</script></span></span><span class="u-displayInlineBlock InlineList-item-text"> and <span class="u-textDecorationUnderline u-clickable InlineList-item-text js-work-more-authors-25928715">+4</span><div class="hidden js-additional-users-25928715"><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://independent.academia.edu/JorgeRamirezFranco">Jorge Ramírez-Franco</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm-sk.academia.edu/MagdalenaTorres">Magdalena Torres</a></span></div><div><span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a href="https://ucm.academia.edu/JSanchezprieto">J. Sanchez-prieto</a></span></div></div></span><script>(function(){ var popoverSettings = { el: $('.js-work-more-authors-25928715'), placement: 'bottom', hide_delay: 200, html: true, content: function(){ return $('.js-additional-users-25928715').html(); } } new HoverPopover(popoverSettings); })();</script></li><li class="js-paper-rank-work_25928715 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="25928715"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 25928715, container: ".js-paper-rank-work_25928715", }); });</script></li><li class="js-percentile-work_25928715 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 25928715; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_25928715"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_25928715 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="25928715"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 25928715; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=25928715]").text(description); $(".js-view-count-work_25928715").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_25928715").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="25928715"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">15</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="18529" href="https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents">Fluorescent Dyes and Reagents</a>, <script data-card-contents-for-ri="18529" type="text/json">{"id":18529,"name":"Fluorescent Dyes and Reagents","url":"https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="47884" href="https://www.academia.edu/Documents/in/Biological_Sciences">Biological Sciences</a>, <script data-card-contents-for-ri="47884" type="text/json">{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="57818" href="https://www.academia.edu/Documents/in/Tacrolimus">Tacrolimus</a>, <script data-card-contents-for-ri="57818" type="text/json">{"id":57818,"name":"Tacrolimus","url":"https://www.academia.edu/Documents/in/Tacrolimus","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="65615" href="https://www.academia.edu/Documents/in/Cerebellum">Cerebellum</a><script data-card-contents-for-ri="65615" type="text/json">{"id":65615,"name":"Cerebellum","url":"https://www.academia.edu/Documents/in/Cerebellum","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=25928715]'), work: {"id":25928715,"title":"Efficient synaptic vesicle recycling after intense exocytosis concomitant with the accumulation of non-releasable endosomes at early developmental stages","created_at":"2016-06-06T11:10:55.282-07:00","owner_id":49637377,"url":"https://www.academia.edu/25928715/Efficient_synaptic_vesicle_recycling_after_intense_exocytosis_concomitant_with_the_accumulation_of_non_releasable_endosomes_at_early_developmental_stages","slug":"Efficient_synaptic_vesicle_recycling_after_intense_exocytosis_concomitant_with_the_accumulation_of_non_releasable_endosomes_at_early_developmental_stages","dom_id":"work_25928715","summary":"Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture increased the proportion of synaptic boutons that were capable of an intense release response, whereas the chronic blockage of synaptic activity diminished the capacity of boutons to release dye. by either a weak or a strong loss of FM1-43. Endocytosis in both subsets of nerve terminals was sensitive to the dynamin inhibitor dynasore, which completely prevented dye unloading and dramatically diminished the number of synaptic vesicles. Decreasing the intensity of exocytosis increased the proportion of synaptic boutons that lose large amounts of dye and reduced the presence of endosome-like structures. Together, these findings demonstrate that efficient vesicle-recycling pathways coexist with those pathways that involve the formation of non-releasable endosomes in synaptic boutons, although in different proportions.","publication":"Journal of Cell Science","publication_with_fallback":"Journal of Cell Science","downloadable_attachments":[{"id":46286463,"asset_id":25928715,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/46286463/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/46286463/Efficient_synaptic_vesicle_recycling_aft20160606-32635-tzrg7u-libre.pdf?1465237020=\u0026response-content-disposition=attachment%3B+filename%3DEfficient_synaptic_vesicle_recycling_aft.pdf\u0026Expires=1734129016\u0026Signature=HPIar47AotgLqFIlnBNrfI7HGMmRNe9SL~IqA20t4mG5WNuhmiEWYiwE9BDW6appK6bVYrj3hXPBe~9peVi3tJUdA3MgqrQRYNUmysPaprioTyPOOJLs68WOgpqXBFHiEE1z7b1T6nfPLOH6fLcOET21nAvQfCGK3mUpGKEbDGsgMtS-0G8RdaqxhAkfkg4JqLw1Zump-HxklFv7Cxne1-EALe5RDYqHdzJWlZlJar~7xnAYrnbqbve0KHvIwkIUncvtiUZa2eWrhY7w0G8TPO35EHYrKUOdd-8m5Cak2SNetKXw729H2JVm-tDXoa1gqvNGkGkALLa7S5rTOcYwlA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/46286463/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/46286463/mini_magick20190210-27070-d3q51p.png?1549799882"}],"downloadable_attachments_with_full_thumbnails":[{"id":46286463,"asset_id":25928715,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/46286463/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/46286463/Efficient_synaptic_vesicle_recycling_aft20160606-32635-tzrg7u-libre.pdf?1465237020=\u0026response-content-disposition=attachment%3B+filename%3DEfficient_synaptic_vesicle_recycling_aft.pdf\u0026Expires=1734129016\u0026Signature=HPIar47AotgLqFIlnBNrfI7HGMmRNe9SL~IqA20t4mG5WNuhmiEWYiwE9BDW6appK6bVYrj3hXPBe~9peVi3tJUdA3MgqrQRYNUmysPaprioTyPOOJLs68WOgpqXBFHiEE1z7b1T6nfPLOH6fLcOET21nAvQfCGK3mUpGKEbDGsgMtS-0G8RdaqxhAkfkg4JqLw1Zump-HxklFv7Cxne1-EALe5RDYqHdzJWlZlJar~7xnAYrnbqbve0KHvIwkIUncvtiUZa2eWrhY7w0G8TPO35EHYrKUOdd-8m5Cak2SNetKXw729H2JVm-tDXoa1gqvNGkGkALLa7S5rTOcYwlA__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/46286463/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/46286463/mini_magick20190210-27070-d3q51p.png?1549799882"}],"has_pdf":true,"has_fulltext":true,"page_count":13,"ordered_authors":[{"id":49637377,"first_name":"David","last_name":"Bartolomé-Martín","domain_name":"uam","page_name":"DavidBartoloméMartín","display_name":"David Bartolomé-Martín","profile_url":"https://uam.academia.edu/DavidBartolom%C3%A9Mart%C3%ADn","photo":"/images/s65_no_pic.png"},{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"},{"id":47199846,"first_name":"Jorge","last_name":"Ramírez-Franco","domain_name":"independent","page_name":"JorgeRamirezFranco","display_name":"Jorge Ramírez-Franco","profile_url":"https://independent.academia.edu/JorgeRamirezFranco","photo":"/images/s65_no_pic.png"},{"id":38011380,"first_name":"Magdalena","last_name":"Torres","domain_name":"ucm-sk","page_name":"MagdalenaTorres","display_name":"Magdalena Torres","profile_url":"https://ucm-sk.academia.edu/MagdalenaTorres","photo":"/images/s65_no_pic.png"},{"id":38118709,"first_name":"J.","last_name":"Sanchez-prieto","domain_name":"ucm","page_name":"JSanchezprieto","display_name":"J. Sanchez-prieto","profile_url":"https://ucm.academia.edu/JSanchezprieto","photo":"/images/s65_no_pic.png"}],"research_interests":[{"id":18529,"name":"Fluorescent Dyes and Reagents","url":"https://www.academia.edu/Documents/in/Fluorescent_Dyes_and_Reagents","nofollow":false},{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences","nofollow":false},{"id":57818,"name":"Tacrolimus","url":"https://www.academia.edu/Documents/in/Tacrolimus","nofollow":false},{"id":65615,"name":"Cerebellum","url":"https://www.academia.edu/Documents/in/Cerebellum","nofollow":false},{"id":90156,"name":"Endocytosis","url":"https://www.academia.edu/Documents/in/Endocytosis"},{"id":107533,"name":"Cell","url":"https://www.academia.edu/Documents/in/Cell"},{"id":182193,"name":"Synaptic Vesicle Recycling","url":"https://www.academia.edu/Documents/in/Synaptic_Vesicle_Recycling"},{"id":267008,"name":"FM","url":"https://www.academia.edu/Documents/in/FM"},{"id":375054,"name":"Rats","url":"https://www.academia.edu/Documents/in/Rats"},{"id":557707,"name":"Exocytosis","url":"https://www.academia.edu/Documents/in/Exocytosis"},{"id":564879,"name":"Wistar Rats","url":"https://www.academia.edu/Documents/in/Wistar_Rats"},{"id":917174,"name":"Calcineurin inhibitors","url":"https://www.academia.edu/Documents/in/Calcineurin_inhibitors"},{"id":955937,"name":"Quaternary Ammonium Compounds","url":"https://www.academia.edu/Documents/in/Quaternary_Ammonium_Compounds"},{"id":1254280,"name":"Endosomes","url":"https://www.academia.edu/Documents/in/Endosomes"},{"id":1654784,"name":"Cerebellar Granule Neuron","url":"https://www.academia.edu/Documents/in/Cerebellar_Granule_Neuron"}],"publication_year":2012,"publication_year_with_fallback":2012,"paper_rank":null,"all_time_views":23,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_36487498" data-work_id="36487498" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/36487498/Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles">Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_36487498" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/36487498" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="c0ec66dfd84f0af28b7529e28902a050" rel="nofollow" data-download="{"attachment_id":56406367,"asset_id":36487498,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/56406367/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_36487498 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="36487498"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 36487498, container: ".js-paper-rank-work_36487498", }); 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$(".js-view-count[data-work-id=36487498]").text(description); $(".js-view-count-work_36487498").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_36487498").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="36487498"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">6</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="161" href="https://www.academia.edu/Documents/in/Neuroscience">Neuroscience</a>, <script data-card-contents-for-ri="161" type="text/json">{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="57556" href="https://www.academia.edu/Documents/in/Hippocampus">Hippocampus</a>, <script data-card-contents-for-ri="57556" type="text/json">{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="62285" href="https://www.academia.edu/Documents/in/Neuropeptides">Neuropeptides</a>, <script data-card-contents-for-ri="62285" type="text/json">{"id":62285,"name":"Neuropeptides","url":"https://www.academia.edu/Documents/in/Neuropeptides","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="1161032" href="https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle">Large Dense Core Vesicle</a><script data-card-contents-for-ri="1161032" type="text/json">{"id":1161032,"name":"Large Dense Core Vesicle","url":"https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=36487498]'), work: {"id":36487498,"title":"Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles","created_at":"2018-04-24T04:35:42.651-07:00","owner_id":43706937,"url":"https://www.academia.edu/36487498/Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles","slug":"Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles","dom_id":"work_36487498","summary":"Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.","publication":null,"publication_with_fallback":"Frontiers in Cellular Neuroscience","downloadable_attachments":[{"id":56406367,"asset_id":36487498,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/56406367/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/56406367/Ramirez-Franco_et_al_Excitatory_and_Inhibitory_Neurons_Dense_Core_Vesicles_FICNS_2016-libre.pdf?1524570140=\u0026response-content-disposition=attachment%3B+filename%3DExcitatory_and_Inhibitory_Neurons_in_the.pdf\u0026Expires=1733461607\u0026Signature=OEYfW6qNf0XH7ndqAVM6DTK4-51D602M-JUrl0EFgvoHj83gxnB7H6sPH8VcKhnQonIGe8FKlCI3aRFPTEvJZPSj9l~IbzjhFdZfuExiTNerZYUekdQ-XaeIFNGucy1~TereUm6Mt6SUc45Zt1hKRdvH6KPkbvzAq1xfzzF087l~9hFAu1~3bgICVBOQfOfqX8X5X~Vwfkp-BNkwBe-OsttIVUo5AtKeY48w4D43VMLTldcx-dLvkTxMHHrK-UomkbrHLDmSJ-4zqApIJRD49E64sJY1zRU0BwBiQjhzw63LGQ2ZFEGYX7vSq~W-31FLRc6xGUCSifZFQVJszlSdog__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/56406367/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/56406367/mini_magick20190112-25870-opd8al.png?1547296584"}],"downloadable_attachments_with_full_thumbnails":[{"id":56406367,"asset_id":36487498,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/56406367/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/56406367/Ramirez-Franco_et_al_Excitatory_and_Inhibitory_Neurons_Dense_Core_Vesicles_FICNS_2016-libre.pdf?1524570140=\u0026response-content-disposition=attachment%3B+filename%3DExcitatory_and_Inhibitory_Neurons_in_the.pdf\u0026Expires=1733461607\u0026Signature=OEYfW6qNf0XH7ndqAVM6DTK4-51D602M-JUrl0EFgvoHj83gxnB7H6sPH8VcKhnQonIGe8FKlCI3aRFPTEvJZPSj9l~IbzjhFdZfuExiTNerZYUekdQ-XaeIFNGucy1~TereUm6Mt6SUc45Zt1hKRdvH6KPkbvzAq1xfzzF087l~9hFAu1~3bgICVBOQfOfqX8X5X~Vwfkp-BNkwBe-OsttIVUo5AtKeY48w4D43VMLTldcx-dLvkTxMHHrK-UomkbrHLDmSJ-4zqApIJRD49E64sJY1zRU0BwBiQjhzw63LGQ2ZFEGYX7vSq~W-31FLRc6xGUCSifZFQVJszlSdog__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/56406367/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/56406367/mini_magick20190112-25870-opd8al.png?1547296584"}],"has_pdf":true,"has_fulltext":true,"page_count":17,"ordered_authors":[{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience","nofollow":false},{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus","nofollow":false},{"id":62285,"name":"Neuropeptides","url":"https://www.academia.edu/Documents/in/Neuropeptides","nofollow":false},{"id":1161032,"name":"Large Dense Core Vesicle","url":"https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle","nofollow":false},{"id":1287048,"name":"Interneurons","url":"https://www.academia.edu/Documents/in/Interneurons"},{"id":2941416,"name":"Chromogranin B","url":"https://www.academia.edu/Documents/in/Chromogranin_B"}],"publication_year":null,"publication_year_with_fallback":2016,"paper_rank":null,"all_time_views":23,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_58986302" data-work_id="58986302" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/58986302/beta_Adrenergic_Receptors_Activate_Exchange_Protein_Directly_Activated_by_cAMP_Epac_Translocate_Munc13_1_and_Enhance_the_Rab3A_RIM1_alpha_Interaction_to_Potentiate_Glutamate_Release_at_Cerebrocortical_Nerve_Terminals">beta-Adrenergic Receptors Activate Exchange Protein Directly Activated by cAMP (Epac), Translocate Munc13-1, and Enhance the Rab3A-RIM1 alpha Interaction to Potentiate Glutamate Release at Cerebrocortical Nerve Terminals</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Background: G protein-coupled receptors generating cAMP at nerve terminals modulate neurotransmitter release. Results: ␤-Adrenergic receptor enhances glutamate release via Epac protein activation and Munc13-1 translocation at... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_58986302" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Background: G protein-coupled receptors generating cAMP at nerve terminals modulate neurotransmitter release. Results: ␤-Adrenergic receptor enhances glutamate release via Epac protein activation and Munc13-1 translocation at cerebrocortical nerve terminals. Conclusion: Protein kinase A-independent signaling pathways triggered by ␤-adrenergic receptors control presynaptic function. Significance: ␤-Adrenergic receptors target presynaptic release machinery. The adenylyl cyclase activator forskolin facilitates synaptic transmission presynaptically via cAMP-dependent protein kinase (PKA). In addition, cAMP also increases glutamate release via PKA-independent mechanisms, although the downstream presynaptic targets remain largely unknown. Here, we describe the isolation of a PKA-independent component of glutamate release in cerebrocortical nerve terminals after blocking Na ؉ channels with tetrodotoxin. We found that 8-pCPT-2-O-Me-cAMP, a specific activator of the exchange protein directly activated by cAMP (Epac), mimicked and occluded forskolininduced potentiation of glutamate release. This Epac-mediated increase in glutamate release was dependent on phospholipase C, and it increased the hydrolysis of phosphatidylinositol 4,5bisphosphate. Moreover, the potentiation of glutamate release by Epac was independent of protein kinase C, although it was attenuated by the diacylglycerol-binding site antagonist calphostin C. Epac activation translocated the active zone protein Munc13-1 from soluble to particulate fractions; it increased the association between Rab3A and RIM1␣ and redistributed synaptic vesicles closer to the presynaptic membrane. Furthermore, these responses were mimicked by the ␤-adrenergic receptor (␤AR) agonist isoproterenol, consistent with the immunoelectron microscopy and immunocytochemical data demonstrating presynaptic expression of ␤ARs in a subset of glutamatergic synapses in the cerebral cortex. Based on these findings, we conclude that ␤ARs couple to a cAMP/Epac/PLC/Munc13/Rab3/ RIM-dependent pathway to enhance glutamate release at cerebrocortical nerve terminals. * This work was supported by Spanish Ministerio de Educación y Ciencia Grants BFU2010-16947 (to J. S.-P.) and SAF2011-24779 and CSD2008-00005 (to F. C.) and CONSOLIDER (CSD2008-00005) (to R. L. and F. C.), Instituto de Salud Carlos III Grants RD06/0026 and RD12/0014, and Comunidad de Madrid Grant CAM-I2M2 2011-BMD-2349 (to J. S.-P. and M. T.). 1 Recipient of an FPU fellowship from the Spanish Ministerio Educació n, Cultura y Deporte (MECD).</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/58986302" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="b2c6268e48a2742198895b08ae87a836" rel="nofollow" data-download="{"attachment_id":73132034,"asset_id":58986302,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/73132034/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_58986302 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="58986302"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 58986302, container: ".js-paper-rank-work_58986302", }); 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$(".js-view-count[data-work-id=58986302]").text(description); $(".js-view-count-work_58986302").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_58986302").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="58986302"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">13</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="12981" href="https://www.academia.edu/Documents/in/Enzyme_Inhibitors">Enzyme Inhibitors</a>, <script data-card-contents-for-ri="12981" type="text/json">{"id":12981,"name":"Enzyme Inhibitors","url":"https://www.academia.edu/Documents/in/Enzyme_Inhibitors","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="18520" href="https://www.academia.edu/Documents/in/Biological_Chemistry">Biological Chemistry</a>, <script data-card-contents-for-ri="18520" type="text/json">{"id":18520,"name":"Biological Chemistry","url":"https://www.academia.edu/Documents/in/Biological_Chemistry","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="47884" href="https://www.academia.edu/Documents/in/Biological_Sciences">Biological Sciences</a>, <script data-card-contents-for-ri="47884" type="text/json">{"id":47884,"name":"Biological Sciences","url":"https://www.academia.edu/Documents/in/Biological_Sciences","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="78467" href="https://www.academia.edu/Documents/in/Cerebral_Cortex">Cerebral Cortex</a><script data-card-contents-for-ri="78467" type="text/json">{"id":78467,"name":"Cerebral Cortex","url":"https://www.academia.edu/Documents/in/Cerebral_Cortex","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=58986302]'), work: {"id":58986302,"title":"beta-Adrenergic Receptors Activate Exchange Protein Directly Activated by cAMP (Epac), Translocate Munc13-1, and Enhance the Rab3A-RIM1 alpha Interaction to Potentiate Glutamate Release at Cerebrocortical Nerve Terminals","created_at":"2021-10-19T02:05:40.775-07:00","owner_id":43706937,"url":"https://www.academia.edu/58986302/beta_Adrenergic_Receptors_Activate_Exchange_Protein_Directly_Activated_by_cAMP_Epac_Translocate_Munc13_1_and_Enhance_the_Rab3A_RIM1_alpha_Interaction_to_Potentiate_Glutamate_Release_at_Cerebrocortical_Nerve_Terminals","slug":"beta_Adrenergic_Receptors_Activate_Exchange_Protein_Directly_Activated_by_cAMP_Epac_Translocate_Munc13_1_and_Enhance_the_Rab3A_RIM1_alpha_Interaction_to_Potentiate_Glutamate_Release_at_Cerebrocortical_Nerve_Terminals","dom_id":"work_58986302","summary":"Background: G protein-coupled receptors generating cAMP at nerve terminals modulate neurotransmitter release. Results: ␤-Adrenergic receptor enhances glutamate release via Epac protein activation and Munc13-1 translocation at cerebrocortical nerve terminals. Conclusion: Protein kinase A-independent signaling pathways triggered by ␤-adrenergic receptors control presynaptic function. Significance: ␤-Adrenergic receptors target presynaptic release machinery. The adenylyl cyclase activator forskolin facilitates synaptic transmission presynaptically via cAMP-dependent protein kinase (PKA). In addition, cAMP also increases glutamate release via PKA-independent mechanisms, although the downstream presynaptic targets remain largely unknown. Here, we describe the isolation of a PKA-independent component of glutamate release in cerebrocortical nerve terminals after blocking Na ؉ channels with tetrodotoxin. We found that 8-pCPT-2-O-Me-cAMP, a specific activator of the exchange protein directly activated by cAMP (Epac), mimicked and occluded forskolininduced potentiation of glutamate release. This Epac-mediated increase in glutamate release was dependent on phospholipase C, and it increased the hydrolysis of phosphatidylinositol 4,5bisphosphate. Moreover, the potentiation of glutamate release by Epac was independent of protein kinase C, although it was attenuated by the diacylglycerol-binding site antagonist calphostin C. Epac activation translocated the active zone protein Munc13-1 from soluble to particulate fractions; it increased the association between Rab3A and RIM1␣ and redistributed synaptic vesicles closer to the presynaptic membrane. Furthermore, these responses were mimicked by the ␤-adrenergic receptor (␤AR) agonist isoproterenol, consistent with the immunoelectron microscopy and immunocytochemical data demonstrating presynaptic expression of ␤ARs in a subset of glutamatergic synapses in the cerebral cortex. 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class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_60938797" data-work_id="60938797" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/60938797/The_regulation_of_synaptic_vesicle_recycling_by_cGMP_dependent_protein_kinase_type_II_in_cerebellar_granule_cells_under_strong_and_sustained_stimulation">The regulation of synaptic vesicle recycling by cGMP-dependent protein kinase type II in cerebellar granule cells under strong and sustained stimulation</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">From the early periods of neurogenesis and migration, up until synaptogenesis, both nitric oxide (NO) and its downstream messenger, cGMP, are thought to influence the development of neurons. The NO/cGMP/cGMP-dependent protein kinase (cGK)... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_60938797" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">From the early periods of neurogenesis and migration, up until synaptogenesis, both nitric oxide (NO) and its downstream messenger, cGMP, are thought to influence the development of neurons. The NO/cGMP/cGMP-dependent protein kinase (cGK) pathway regulates the clustering and recruitment of synaptic proteins and vesicles to the synapse, adjusting the exoendocytic cycle to the intensity of activity and accelerating endocytosis following large-scale exocytosis. Here, we show that blockage of the N-methyl-D-aspartate receptor impairs the cycling of synaptic vesicles in a subset of boutons on cerebellar granule cells, an effect that was reversed by increasing cGMP. Furthermore, we demonstrate that presynaptic cGK type II (cGKII) plays a major role in this process. Using the FM1-43 dye to track vesicle recycling, we found that knockdown of cGKII and/or the application of a cGK inhibitor reduced the efficiency of synaptic vesicle recycling to a similar extent. Likewise, in cerebellar granu...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/60938797" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="79f2dcda449c6b644f8b57c5214cda4b" rel="nofollow" data-download="{"attachment_id":74163709,"asset_id":60938797,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/74163709/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_60938797 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="60938797"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 60938797, container: ".js-paper-rank-work_60938797", }); 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Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"publication_year":2014,"publication_year_with_fallback":2014,"paper_rank":null,"all_time_views":5,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_73470278" data-work_id="73470278" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/73470278/Cannabinoid_type_1_receptors_transiently_silence_glutamatergic_nerve_terminals_of_cultured_cerebellar_granule_cells">Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_73470278" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Cannabinoid receptors are the most abundant G protein-coupled receptors in the brain and they mediate retrograde short-term inhibition of neurotransmitter release, as well as long-term depression of synaptic transmission at many excitatory synapses. The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchan...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/73470278" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="e5b44be93a0145bddb7ef839dc90d4d2" rel="nofollow" data-download="{"attachment_id":83862456,"asset_id":73470278,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/83862456/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_73470278 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="73470278"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 73470278, container: ".js-paper-rank-work_73470278", }); 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The induction of presynaptically silent synapses is a means of modulating synaptic strength, which is important for synaptic plasticity. Persistent activation of cannabinoid type 1 receptors (CB1Rs) mutes GABAergic terminals, although it is unclear if CB1Rs can also induce silencing at glutamatergic synapses. Cerebellar granule cells were transfected with VGLUT1-pHluorin to visualise the exo-endocytotic cycle. We found that prolonged stimulation (10 min) of cannabinoid receptors with the agonist HU-210 induces the silencing of previously active synapses. However, the presynaptic silencing induced by HU-210 is transient as it reverses after 20 min. cAMP with forskolin prevented CB1R-induced synaptic silencing, via activation of the Exchan...","publication":"PloS one","publication_with_fallback":"PloS 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endosomes at early developmental stages</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557126" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Following the exocytosis of neurotransmitter-containing synaptic vesicles, endocytosis is fundamental to re-establishing conditions for synaptic transmission. As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. 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As there are distinct endocytotic pathways that each differ in their efficiency to generate releasable synaptic vesicles, we used the dye FM1-43 to track vesicle recycling, and to determine whether nerve terminals use multiple pathways of endocytosis. We identified two types of synaptic boutons in cultured cerebellar granule cells that were characterized by weak or strong FM1-43-unloading profiles. Decreasing the extent of exocytosis dramatically increased the proportion of synaptic boutons that exhibited strong FM1-43-unloading and dramatically reduced the number of endosome-like structures. Hence, we concluded that efficient recycling of synaptic vesicles is concomitant with the formation of non-releasable endosomes in both types of synaptic boutons, although to different extents. Furthermore, cell maturation in culture incr...","publication":"Journal of Cell Science","publication_with_fallback":"Journal of Cell 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Compounds","url":"https://www.academia.edu/Documents/in/Quaternary_Ammonium_Compounds"},{"id":1254280,"name":"Endosomes","url":"https://www.academia.edu/Documents/in/Endosomes"},{"id":1654784,"name":"Cerebellar Granule Neuron","url":"https://www.academia.edu/Documents/in/Cerebellar_Granule_Neuron"},{"id":3276666,"name":"fluorescent dyes","url":"https://www.academia.edu/Documents/in/fluorescent_dyes"},{"id":3763225,"name":"Medical and Health Sciences","url":"https://www.academia.edu/Documents/in/Medical_and_Health_Sciences"}],"publication_year":2012,"publication_year_with_fallback":2012,"paper_rank":null,"all_time_views":4,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_74557127" data-work_id="74557127" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/74557127/Daidzein_has_neuroprotective_effects_through_ligand_binding_independent_PPAR%CE%B3_activation">Daidzein has neuroprotective effects through ligand-binding-independent PPARγ activation</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557127" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Phytoestrogens are a group of plant-derived compounds that include mainly isoflavones like daidzein. Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-c (PPARc), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARc. Our results show that daidzein (0.05-5 lM) decreases cell death induced by exposure to oxygen-glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARc antagonist T0070907 (1 lM). In addition, this phytoestrogen activated PPARc in neuronal cultures, as shown by an increase in PPARc transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARc competitive binding assay. Conversely, daidzein increased PPARc nuclear protein levels and decreased cytosolic ones, suggesting nuclear translocation. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARc activity not mediated by direct binding to the receptor ligandbinding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/74557127" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="df534a01a3f5bd988ba94de29873d894" rel="nofollow" data-download="{"attachment_id":83761624,"asset_id":74557127,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/83761624/download_file?st=MTczNDEzMTI3Miw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_74557127 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="74557127"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 74557127, container: ".js-paper-rank-work_74557127", }); 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Phytoestrogens prevent neuronal damage and improve outcome in experimental stroke; however, the mechanisms of this neuroprotective action have not been fully elucidated. In this context, it has been postulated that phytoestrogens might activate the peroxisome proliferator-activated receptor-c (PPARc), which exerts neuroprotective effects in several settings. The aim of this study was to determine whether the phytoestrogen daidzein elicits beneficial actions in neuronal cells by mechanisms involving activation of PPARc. Our results show that daidzein (0.05-5 lM) decreases cell death induced by exposure to oxygen-glucose deprivation (OGD) from rat cortical neurons and that improves synaptic function, in terms of increased synaptic vesicle recycling at nerve terminals, being both effects inhibited by the PPARc antagonist T0070907 (1 lM). In addition, this phytoestrogen activated PPARc in neuronal cultures, as shown by an increase in PPARc transcriptional activity. Interestingly, these effects were not due to binding to the receptor ligand site, as shown by a TR-FRET PPARc competitive binding assay. Conversely, daidzein increased PPARc nuclear protein levels and decreased cytosolic ones, suggesting nuclear translocation. We have used the receptor antagonist (RE) fulvestrant to study the neuroprotective participation of daidzein via estrogen receptor and at least in our model, we have discarded this pathway. These results demonstrate that the phytoestrogen daidzein has cytoprotective properties in neurons, which are due to an increase in PPARc activity not mediated by direct binding to the receptor ligandbinding domain but likely due to post-translational modifications affecting its subcellular location and not depending to the RE and it is not additive with the agonist rosiglitazone.","publication":"Neurochemistry International","publication_with_fallback":"Neurochemistry 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metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell-and synapse-specificity of the functional relationship... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557128" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Astrocytes are important regulatory elements in brain function. They respond to neurotransmitters and release gliotransmitters that modulate synaptic transmission. However, the cell-and synapse-specificity of the functional relationship between astrocytes and neurons in certain brain circuits remains unknown. In the dorsal striatum, which mainly comprises two intermingled subtypes (striatonigral and striatopallidal) of medium spiny neurons (MSNs) and synapses belonging to two neural circuits (the direct and indirect pathways of the basal ganglia), subpopulations of astrocytes selectively responded to specific MSN subtype activity. These subpopulations of astrocytes released glutamate that selectively activated N-methyl-D-aspartate receptors in homotypic, but not heterotypic, MSNs. Likewise, astrocyte subpopulations selectively regulated homotypic synapses through metabotropic glutamate receptor activation. The results I will present in this seminar show that bidirectional astrocyte-neuron signaling selectively occurs between specific subpopulations of astrocytes, neurons, and synapses.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/74557128" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="7d96572f5220afef29b7b26a8c35781c" rel="nofollow" data-download="{"attachment_id":82666939,"asset_id":74557128,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/82666939/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_74557128 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="74557128"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 74557128, container: ".js-paper-rank-work_74557128", }); 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$(".js-view-count[data-work-id=74557128]").text(description); $(".js-view-count-work_74557128").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_74557128").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="74557128"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">17</a>  </div><span class="InlineList-item-text u-textTruncate u-pl10x"><a class="InlineList-item-text" data-has-card-for-ri="221" href="https://www.academia.edu/Documents/in/Psychology">Psychology</a>, <script data-card-contents-for-ri="221" type="text/json">{"id":221,"name":"Psychology","url":"https://www.academia.edu/Documents/in/Psychology","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="7955" href="https://www.academia.edu/Documents/in/Neuropharmacology">Neuropharmacology</a>, <script data-card-contents-for-ri="7955" type="text/json">{"id":7955,"name":"Neuropharmacology","url":"https://www.academia.edu/Documents/in/Neuropharmacology","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="38831" href="https://www.academia.edu/Documents/in/Signal_Transduction">Signal Transduction</a>, <script data-card-contents-for-ri="38831" type="text/json">{"id":38831,"name":"Signal Transduction","url":"https://www.academia.edu/Documents/in/Signal_Transduction","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="65615" href="https://www.academia.edu/Documents/in/Cerebellum">Cerebellum</a><script data-card-contents-for-ri="65615" type="text/json">{"id":65615,"name":"Cerebellum","url":"https://www.academia.edu/Documents/in/Cerebellum","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=74557128]'), work: {"id":74557128,"title":"Cross-talk between metabotropic glutamate receptor 7 and beta adrenergic receptor signaling at cerebrocortical nerve terminals","created_at":"2022-03-25T09:36:51.342-07:00","owner_id":43706937,"url":"https://www.academia.edu/74557128/Cross_talk_between_metabotropic_glutamate_receptor_7_and_beta_adrenergic_receptor_signaling_at_cerebrocortical_nerve_terminals","slug":"Cross_talk_between_metabotropic_glutamate_receptor_7_and_beta_adrenergic_receptor_signaling_at_cerebrocortical_nerve_terminals","dom_id":"work_74557128","summary":"Astrocytes are important regulatory elements in brain function. 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u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Synaptic transmission in the mammalian nervous system is mainly based on chemical synapses. These synapses contain a cluster of small vesicles that are filled up with neurotransmitter molecules, referred to as synaptic vesicles (SVs)... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557129" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Synaptic transmission in the mammalian nervous system is mainly based on chemical synapses. These synapses contain a cluster of small vesicles that are filled up with neurotransmitter molecules, referred to as synaptic vesicles (SVs) (Sudhof, 2012). Upon the arrival of an action potential to the presynaptic compartment, calcium influx through voltage gated calcium channels (VGCC) promotes the fussion of these SVs with the plasma membrane, leading to the release of the neurotransmitter into the synaptic cleft (Sudhof, 2004). Once in the extracellular space neurotransmitter molecules bind to postsynaptic receptors (Attwell y Gibb, 2005), propagating, in this way, the nerve impulse through neuronal networks. The released neurotransmitter can also activate presynaptic receptors which, in turn, modulates neurotransmitter release. Axonal sites of neurotransmitter release, also known as Active Zones (AZs), contain a high density of VGCC sorrounded by a complex network of proteins that inte...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/74557129" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="86b999569ca36393dfb5514dc8a3e71b" rel="nofollow" data-download="{"attachment_id":83759603,"asset_id":74557129,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/83759603/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_74557129 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="74557129"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 74557129, container: ".js-paper-rank-work_74557129", }); });</script></li><li class="js-percentile-work_74557129 InlineList-item InlineList-item--bordered hidden u-tcGrayDark"><span class="percentile-widget hidden"><span class="u-mr2x percentile-widget" style="display: none">•</span><span class="u-mr2x work-percentile"></span></span><script>$(function () { var workId = 74557129; window.Academia.workPercentilesFetcher.queue(workId, function (percentileText) { var container = $(".js-percentile-work_74557129"); container.find('.work-percentile').text(percentileText.charAt(0).toUpperCase() + percentileText.slice(1)); container.find('.percentile-widget').show(); container.find('.percentile-widget').removeClass('hidden'); }); });</script></li><li class="js-view-count-work_74557129 InlineList-item InlineList-item--bordered hidden"><div><span><span class="js-view-count view-count u-mr2x" data-work-id="74557129"><i class="fa fa-spinner fa-spin"></i></span><script>$(function () { var workId = 74557129; window.Academia.workViewCountsFetcher.queue(workId, function (count) { var description = window.$h.commaizeInt(count) + " " + window.$h.pluralize(count, 'View'); $(".js-view-count[data-work-id=74557129]").text(description); $(".js-view-count-work_74557129").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_74557129").removeClass('hidden') })</script></div></li></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_74557130" data-work_id="74557130" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/74557130/Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles">Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557130" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/74557130" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="5574469cfce2c724300ffb464d6f7b20" rel="nofollow" data-download="{"attachment_id":82666930,"asset_id":74557130,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/82666930/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_74557130 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="74557130"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 74557130, container: ".js-paper-rank-work_74557130", }); 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$(".js-view-count[data-work-id=74557130]").text(description); $(".js-view-count-work_74557130").attr('title', description).tooltip(); }); });</script></span><script>$(function() { $(".js-view-count-work_74557130").removeClass('hidden') })</script></div></li><li class="InlineList-item u-positionRelative" style="max-width: 250px"><div class="u-positionAbsolute" data-has-card-for-ri-list="74557130"><i class="fa fa-tag InlineList-item-icon u-positionRelative"></i>  <a class="InlineList-item-text u-positionRelative">6</a>  </div><span class="InlineList-item-text u-textTruncate u-pl9x"><a class="InlineList-item-text" data-has-card-for-ri="161" href="https://www.academia.edu/Documents/in/Neuroscience">Neuroscience</a>, <script data-card-contents-for-ri="161" type="text/json">{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="57556" href="https://www.academia.edu/Documents/in/Hippocampus">Hippocampus</a>, <script data-card-contents-for-ri="57556" type="text/json">{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="62285" href="https://www.academia.edu/Documents/in/Neuropeptides">Neuropeptides</a>, <script data-card-contents-for-ri="62285" type="text/json">{"id":62285,"name":"Neuropeptides","url":"https://www.academia.edu/Documents/in/Neuropeptides","nofollow":false}</script><a class="InlineList-item-text" data-has-card-for-ri="1161032" href="https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle">Large Dense Core Vesicle</a><script data-card-contents-for-ri="1161032" type="text/json">{"id":1161032,"name":"Large Dense Core Vesicle","url":"https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle","nofollow":false}</script></span></li><script>(function(){ if (true) { new Aedu.ResearchInterestListCard({ el: $('*[data-has-card-for-ri-list=74557130]'), work: {"id":74557130,"title":"Excitatory and Inhibitory Neurons in the Hippocampus Exhibit Molecularly Distinct Large Dense Core Vesicles","created_at":"2022-03-25T09:36:51.718-07:00","owner_id":43706937,"url":"https://www.academia.edu/74557130/Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles","slug":"Excitatory_and_Inhibitory_Neurons_in_the_Hippocampus_Exhibit_Molecularly_Distinct_Large_Dense_Core_Vesicles","dom_id":"work_74557130","summary":"Hippocampal interneurons comprise a diverse family of inhibitory neurons that are critical for detailed information processing. Along with gamma-aminobutyric acid (GABA), interneurons secrete a myriad of neuroactive substances via secretory vesicles but the molecular composition and regulatory mechanisms remain largely unknown. In this study, we have carried out an immunohistofluorescence analysis to describe the molecular content of vesicles in distinct populations of hippocampal neurons. Our results indicate that phogrin, an integral protein of secretory vesicles in neuroendocrine cells, is highly enriched in parvalbumin-positive interneurons. Consistently, immunoelectron microscopy revealed phogrin staining in axon terminals of symmetrical synapses establishing inhibitory contacts with cell bodies of CA1 pyramidal neurons. Furthermore, phogrin is highly expressed in CA3 and dentate gyrus (DG) interneurons which are both positive for PV and neuropeptide Y. Surprisingly, chromogranin B a canonical large dense core vesicle marker, is excluded from inhibitory cells in the hippocampus but highly expressed in excitatory CA3 pyramidal neurons and DG granule cells. Our results provide the first evidence of phogrin expression in hippocampal interneurons and suggest the existence of molecularly distinct populations of secretory vesicles in different types of inhibitory neurons.","publication":"Frontiers in Cellular Neuroscience","publication_with_fallback":"Frontiers in Cellular Neuroscience","downloadable_attachments":[{"id":82666930,"asset_id":74557130,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/82666930/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/82666930/3bb0882ff1b263aac9b331336d5b9db0b775-libre.pdf?1648226441=\u0026response-content-disposition=attachment%3B+filename%3DExcitatory_and_Inhibitory_Neurons_in_the.pdf\u0026Expires=1733571874\u0026Signature=MdLtt-oPTPujOli2scCBzFoO9h95Coihhkyl8VOJAMgDXJZpcwE~uWKuGTu2wOhqmdWhVm3G1HgRGGPSSNrrGvDpX~3ZHk~8S1ff3CvF7bldzfoCESrfUCSB8-Mfp1o0vUEXPhAHka424C763y73lKxHdDQz6rnJ28idLwrRLw1oy9dJXX~w3glIWQUHSKFMfimuxi-tQeTM2oYqghkwPcm8GbJs3MxiS780~c885-H4dKm2sTye5q9yJ-Qx9aVADKoGV40M3DUtLNxMoeOd~gHQycjLJtaRdiVMgZoF~~u0Qo-E2nO4kSj7WekDIi40lkjNC56weGT12CBUqjuFUQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/82666930/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/82666930/mini_magick20220325-8913-k4w01h.png?1648226436"}],"downloadable_attachments_with_full_thumbnails":[{"id":82666930,"asset_id":74557130,"asset_type":"Work","always_allow_download":false,"scribd_thumbnail_url":"https://attachments.academia-assets.com/82666930/thumbnails/1.jpg","download_url":"https://d1wqtxts1xzle7.cloudfront.net/82666930/3bb0882ff1b263aac9b331336d5b9db0b775-libre.pdf?1648226441=\u0026response-content-disposition=attachment%3B+filename%3DExcitatory_and_Inhibitory_Neurons_in_the.pdf\u0026Expires=1733571874\u0026Signature=MdLtt-oPTPujOli2scCBzFoO9h95Coihhkyl8VOJAMgDXJZpcwE~uWKuGTu2wOhqmdWhVm3G1HgRGGPSSNrrGvDpX~3ZHk~8S1ff3CvF7bldzfoCESrfUCSB8-Mfp1o0vUEXPhAHka424C763y73lKxHdDQz6rnJ28idLwrRLw1oy9dJXX~w3glIWQUHSKFMfimuxi-tQeTM2oYqghkwPcm8GbJs3MxiS780~c885-H4dKm2sTye5q9yJ-Qx9aVADKoGV40M3DUtLNxMoeOd~gHQycjLJtaRdiVMgZoF~~u0Qo-E2nO4kSj7WekDIi40lkjNC56weGT12CBUqjuFUQ__\u0026Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA","download_file_url":"https://www.academia.edu/attachments/82666930/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&","full_thumbnail_url":"https://0.academia-photos.com/attachment_thumbnails/82666930/mini_magick20220325-8913-k4w01h.png?1648226436"}],"has_pdf":true,"has_fulltext":true,"page_count":17,"ordered_authors":[{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}],"research_interests":[{"id":161,"name":"Neuroscience","url":"https://www.academia.edu/Documents/in/Neuroscience","nofollow":false},{"id":57556,"name":"Hippocampus","url":"https://www.academia.edu/Documents/in/Hippocampus","nofollow":false},{"id":62285,"name":"Neuropeptides","url":"https://www.academia.edu/Documents/in/Neuropeptides","nofollow":false},{"id":1161032,"name":"Large Dense Core Vesicle","url":"https://www.academia.edu/Documents/in/Large_Dense_Core_Vesicle","nofollow":false},{"id":1287048,"name":"Interneurons","url":"https://www.academia.edu/Documents/in/Interneurons"},{"id":2941416,"name":"Chromogranin B","url":"https://www.academia.edu/Documents/in/Chromogranin_B"}],"publication_year":2016,"publication_year_with_fallback":2016,"paper_rank":null,"all_time_views":2,"active_discussion":{}}, }) } })();</script></ul></li></ul></div></div><div class="u-borderBottom1 u-borderColorGrayLighter"><div class="clearfix u-pv7x u-mb0x js-work-card work_74557131" data-work_id="74557131" itemscope="itemscope" itemtype="https://schema.org/ScholarlyArticle"><div class="header"><div class="title u-fontSerif u-fs22 u-lineHeight1_3"><a class="u-tcGrayDarkest js-work-link" href="https://www.academia.edu/74557131/Gangliosides_interact_with_synaptotagmin_to_form_the_high_affinity_receptor_complex_for_botulinum_neurotoxin_B">Gangliosides interact with synaptotagmin to form the high-affinity receptor complex for botulinum neurotoxin B</a></div></div><div class="u-pb4x u-mt3x"><div class="summary u-fs14 u-fw300 u-lineHeight1_5 u-tcGrayDarkest"><div class="summarized">Botulinum neurotoxin type B (BoNT/B) recognizes nerve terminals by binding to 2 receptor components: a polysialoganglioside, predominantly GT1b, and synaptotagmin 1/2. It is widely thought that BoNT/B initially binds to GT1b then diffuses... <a class="more_link u-tcGrayDark u-linkUnstyled" data-container=".work_74557131" data-show=".complete" data-hide=".summarized" data-more-link-behavior="true" href="#">more</a></div><div class="complete hidden">Botulinum neurotoxin type B (BoNT/B) recognizes nerve terminals by binding to 2 receptor components: a polysialoganglioside, predominantly GT1b, and synaptotagmin 1/2. It is widely thought that BoNT/B initially binds to GT1b then diffuses in the plane of the membrane to interact with synaptotagmin. We have addressed the hypothesis that a GT1b–synaptotagmin cis complex forms the BoNT/B receptor. We identified a consensus glycosphingolipid-binding motif in the extracellular juxtamembrane domain of synaptotagmins 1/2 and confirmed by Langmuir monolayer, surface plasmon resonance, and circular dichroism that GT1b interacts with synaptotagmin peptides containing this sequence, inducing α-helical structure. Molecular modeling and tryptophan fluorescence spectroscopy were consistent with the intertwining of GT1b and synaptotagmin, involving cis interactions between the oligosaccharide and ceramide moieties of GT1b and the juxtamembrane and transmembrane domains of synaptotagmin, respective...</div></div></div><ul class="InlineList u-ph0x u-fs13"><li class="InlineList-item logged_in_only"><div class="share_on_academia_work_button"><a class="academia_share Button Button--inverseBlue Button--sm js-bookmark-button" data-academia-share="Work/74557131" data-share-source="work_strip" data-spinner="small_white_hide_contents"><i class="fa fa-plus"></i><span class="work-strip-link-text u-ml1x" data-content="button_text">Bookmark</span></a></div></li><li class="InlineList-item"><div class="download"><a id="735a97940c7f21050d8fe993375fca0c" rel="nofollow" data-download="{"attachment_id":82666933,"asset_id":74557131,"asset_type":"Work","always_allow_download":false,"track":null,"button_location":"work_strip","source":null,"hide_modal":null}" class="Button Button--sm Button--inverseGreen js-download-button prompt_button doc_download" href="https://www.academia.edu/attachments/82666933/download_file?st=MTczNDEzMTI3Myw4LjIyMi4yMDguMTQ2&s=work_strip"><i class="fa fa-arrow-circle-o-down fa-lg"></i><span class="u-textUppercase u-ml1x" data-content="button_text">Download</span></a></div></li><li class="InlineList-item"><ul class="InlineList InlineList--bordered u-ph0x"><li class="InlineList-item InlineList-item--bordered"><span class="InlineList-item-text">by <span itemscope="itemscope" itemprop="author" itemtype="https://schema.org/Person"><a class="u-tcGrayDark u-fw700" data-has-card-for-user="43706937" href="https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO">JOSE JORGE RAMIREZ FRANCO</a><script data-card-contents-for-user="43706937" type="text/json">{"id":43706937,"first_name":"JOSE JORGE","last_name":"RAMIREZ FRANCO","domain_name":"otmed","page_name":"JOSEJORGERAMIREZFRANCO","display_name":"JOSE JORGE RAMIREZ FRANCO","profile_url":"https://otmed.academia.edu/JOSEJORGERAMIREZFRANCO","photo":"https://0.academia-photos.com/43706937/12325778/92909930/s65_jose_jorge.ramirez_franco.jpg"}</script></span></span></li><li class="js-paper-rank-work_74557131 InlineList-item InlineList-item--bordered hidden"><span class="js-paper-rank-view hidden u-tcGrayDark" data-paper-rank-work-id="74557131"><i class="u-m1x fa fa-bar-chart"></i><strong class="js-paper-rank"></strong></span><script>$(function() { new Works.PaperRankView({ workId: 74557131, container: ".js-paper-rank-work_74557131", }); 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It is widely thought that BoNT/B initially binds to GT1b then diffuses in the plane of the membrane to interact with synaptotagmin. We have addressed the hypothesis that a GT1b–synaptotagmin cis complex forms the BoNT/B receptor. We identified a consensus glycosphingolipid-binding motif in the extracellular juxtamembrane domain of synaptotagmins 1/2 and confirmed by Langmuir monolayer, surface plasmon resonance, and circular dichroism that GT1b interacts with synaptotagmin peptides containing this sequence, inducing α-helical structure. 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