CINXE.COM

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<p><strong>Chemogenetics</strong> is a powerful and specific method to control and investigate intracellular signaling pathways. Most widely used in neuroscience to control neuronal or glial cell activity, chemogenetic experiments employ compounds that selectively target a genetically-modified <a href='/pharmacology/7-tm-receptors' title='Browse product for GPCRs'>G protein-coupled receptor</a> (GPCR; DREADD) or a chimeric <a href='/pharmacology/ion-channels' title='Browse products for Ion Channels'>ion channel</a> (PSAM).</p> <div class="tabbed_content"> <div class="tab_menu"> <div class="tab tab_1 tab_open" data-tab="1" data-tabname="products" id="pharm_tabs_products"> <span>Targets</span></div> <div class="tab tab_4" data-tab="4" data-tabname="literature" id="pharm_tabs_literature"><span>Literature (3)</span> </div> </div> <div class="tab_content tab_1 tab_open" data-tab="1"> <div class="pharm_sub_cats"><ul class="tile_column_1"><li><a href="/product-type/dreadd-ligands" title="Browse products for DREADD Ligands">DREADD Ligands</a></li></ul><ul class="tile_column_2"><li><a href="/product-type/psems" title="Browse products for PSEMs">PSEMs</a></li></ul></div> <div class="pharm_long_desc"><h2>History of Chemogenetics</h2> <p>GPCRs have been at the forefront of chemogenetic techniques, with the first paper outlining GPCRs that respond only to synthetic ligands published in 1998. These receptors, named Receptors Activated Solely by a Synthetic Ligand (RASSL), were successfully used <em>in vivo</em> to enable control of cardiac activity. However, their use in neuroscience is hampered by the pharmacological activity of the ligands <em>in vivo</em>, and the endogenous, constitutive activity of the engineered receptors in the absence of their specific ligand.</p> <p>More recently, <a href='/product-type/dreadd-ligands' title='View all DREADD Ligands'>Designer Receptors Activated by Designer Drugs</a> (DREADD) have been developed. The first of these were mutated human <a href='/pharmacology/acetylcholine-muscarinic-receptors' title='Browse products for Muscarinic Acetylcholine Receptors'>muscarinic acetylcholine receptors</a> activated solely by inert ligands. Multiple rounds of mutagenesis and ligand screening identified muscarinic receptors coupled to the G<sub>q</sub> intracellular signaling pathway that responded to <a href='/products/clozapine-n-oxide_4936' title='View Clozapine N-Oxide'>Clozapine <em>N</em>-oxide</a> (CNO, Cat. No. 4936). All three G<sub>q</sub> coupled DREADDs (hM<sub>1</sub>D<sub>q</sub>, hM<sub>3</sub>D<sub>q</sub> and hM<sub>5</sub>D<sub>q</sub>) activate neuronal activity in response to binding of a DREADD ligand. The same research identified the inhibitory DREADDs, hM<sub>2</sub>D<sub>i</sub> and hM<sub>4</sub>D<sub>i</sub>, which inhibit neuronal activity in response to DREADD ligand binding. An inhibitory DREADD named KORD, has also been developed from the κ-opioid receptor, which inhibits neuronal activity in response to <a href='/products/salvinorin-b_5611' title='View Salvinorin B'>Salvinorin B</a> (SalB, Cat. No. 5611).</p> <p>The range of chemogenetic tools available to researchers has recently been expanded with the development of chimeric <a href='/pharmacology/ion-channels' title='Browse products for Ion Channels'>ion channels</a>, termed Pharmacologically Selective Actuator Modules (PSAMs), which are selectively bound by compounds termed <a href='/product-type/psems' title='View all PSEMs'>Pharmacologically Selective Effector Molecules</a> (PSEMs). </p> <h2>Chemogenetics vs Optogenetics</h2> <p>Chemogenetic experiments require the introduction of genetically engineered receptors or ion channels into specific brain areas, via viral vector expression systems. <em>In vivo</em> expression of a chemogenetic receptor can be achieved using an Adeno-associated virus (AAV) encoding the DREADD or PSAM, which is then injected into the brain region. The cell-type that the receptor is expressed in can be controlled using cell-type specific genetic promotors. For example, viral DREADD constructs with a <em>CaMKIIa</em> promotor will drive DREADD expression in neurons, while a viral DREADD construct with a <em>GFAP</em> promoter will drive DREADD expression in glia.</p> <p>A similar technique for modulation of neuronal activity is optogenetics, which requires the expression of a light-sensitive ion channel, rather than a <a href='/pharmacology/ligand-gated-ion-channels' title='Browse product for Ligand-gated Ion Channels'>ligand-gated ion channel</a> or GPCR. In optogenetic techniques, activation or inhibition of neuronal activity is initiated by implanted fiber optics, rather than small molecules. The key features of optogenetics and chemogenetics are summarized in the table below.</p> <table class='table'> <thead> <tr> <th>Features</th> <th>Chemogenetics</th> <th>Optogenetics</th> </tr> </thead> <tbody> <tr> <td>Method of intervention</td> <td>Inert, small molecule ligands selective for genetically engineered receptors/ion channels</td> <td>Light-sensitive ion channels activated by implanted fibre optics</td> </tr> <tr> <td>Is the intervention 'physiological'?</td> <td>Yes - uses conserved, intracellular signaling pathways, or changes ion channel conductance, to alter neuronal activity</td> <td>No - patterns of excitation/inhibition are artificially synchronized by light stimulation pattern</td> </tr> <tr> <td>Is the intervention inert?</td> <td>Yes - receptors/ion channels lack pharmacological activity without ligands and ligands are pharmacologically inert without specific engineered receptors/ion channels</td> <td>No - the fibre optic light source can create heat and bacterial light-sensitive channels used can be antigenic</td> </tr> <tr> <td>Is this method invasive <em>in vivo</em>?</td> <td>Minimally to no - ligands can be given by intracerebral infusion, intraperitoneal injection or in drinking water, dependent on specific ligand</td> <td>Yes - inherently invasive due to implantation of fibre optics</td> </tr> <tr> <td>Is specialized equipment required?</td> <td>No</td> <td>Yes - requires implantable fibre optics as light source</td> </tr> </tbody> </table> <h3>Featured Publications Using Tocris DREADD Ligands & PSEMs</h3> <p>Badimon <em>et al</em> (2020) <a href='https://pubmed.ncbi.nlm.nih.gov/32999463/' rel='nofollow' target='_blank'>Negative feedback control of neuronal activity by microglia</a>. Nature <strong>586</strong>, 417. PMID: 32999463</p> <p>Francois <em>et al</em> (2017) <a href='https://pubmed.ncbi.nlm.nih.gov/28162807/' rel='nofollow' target='_blank'>A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins</a>. Neuron <strong>93</strong>, 822. PMID: 28162807</p> <p>Leroy <em>et al</em> (2018) <a href='https://pubmed.ncbi.nlm.nih.gov/30518859/' rel='nofollow' target='_blank'>A circuit from hippocampal CA2 to lateral septum disinhibits social aggression</a>. Nature <strong>564</strong>, 213. PMID: 30518859</p> <p>Nam <em>et al</em> (2019) <a href='https://pubmed.ncbi.nlm.nih.gov/31365861/' rel='nofollow' target='_blank'>Activation of Astrocytic μ-Opioid Receptor Causes Conditioned Place Preference</a>. Cell Rep <strong>28</strong>, 1154. PMID: 31365861</p> <p>Pina <em>et al</em> (2020) <a href='https://pubmed.ncbi.nlm.nih.gov/31870854/' rel='nofollow' target='_blank'>The kappa opioid receptor modulates GABA neuron excitability and synaptic transmission in midbrain-projections from the insular cortex</a>. Neuropharmacology <strong>165</strong>, 107831. PMID: 31870854</p> <h3>References</h3> <p>Campbell & Marchant (2018) <a href='https://pubmed.ncbi.nlm.nih.gov/29338070/' rel='nofollow' target='_blank'>The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats</a>. Br J Pharmacol <strong>175</strong>, 994. PMID: 29338070</p> <p>Coward <em>et al</em> (1998) <a href='https://pubmed.ncbi.nlm.nih.gov/9419379/' rel='nofollow' target='_blank'>Controlling signaling with a specifically designed Gi-coupled receptor</a>. Proc Natl Acad Sci USA <strong>95</strong>, 352. PMID: 9419379</p> <p>Magnus <em>et al</em> (2011) <a href='https://pubmed.ncbi.nlm.nih.gov/21885782/' rel='nofollow' target='_blank'>Chemical and genetic engineering of selective ligand-ion channel interactions</a>. Science <strong>333</strong>, 1292. PMID: 21885782</p> <p>Roth (2016) <a href='https://pubmed.ncbi.nlm.nih.gov/26889809/' rel='nofollow' target='_blank'>DREADDs for Neuroscientists</a>. Neuron <strong>89</strong>, 683. PMID: 26889809</p> <p>Sternson & Roth (2014) <a href='https://pubmed.ncbi.nlm.nih.gov/25002280/' rel='nofollow' target='_blank'>Chemogenetic tools to interrogate brain functions</a>. Annu Rev Neurol <strong>37</strong>, 387. PMID: 25002280</p></div> </div> <div class="tab_content tab_2" data-tab="2"> </div> <div class="tab_content tab_3" data-tab="3"> </div> <div class="tab_content tab_4" data-tab="4"> <h3>Literature for Chemogenetics</h3><p>Tocris offers the following scientific literature for Chemogenetics to showcase our products. We invite you to request* your copy today!</p><p class="small">*Please note that Tocris will only send literature to established scientific business / institute addresses.</p><hr/><div class="lit_item"> <div class="lit_content"> <div class="lit_image"> <a href="https://resources.tocris.com/images/literature/research-bulletins/fullsize/594240.jpg?v=1" data-toggle="lightbox" data-title="Chemogenetics Research Bulletin" data-footer="<a href='/literature/literature-request/p594240' rel='nofollow' title='Request PDF of the Chemogenetics'>Request PDF</a> today"><img loading="lazy" src="https://resources.tocris.com/images/literature/research-bulletins/regular/594240.jpg?v=1" alt="Chemogenetics Research Bulletin" class="img-fluid"></a></div> <h4>Chemogenetics Research Bulletin</h4> <p>Produced by Tocris, the chemogenetics research bulletin provides an introduction to chemogenetic methods to manipulate neuronal activity. It outlines the development of RASSLs, DREADDs and PSAMs, and the use of chemogenetic compounds. DREADD ligands and PSEMs available from Tocris are highlighted.</p> <ul class="pb_lit_buttons"><li> <a class="btn btn-quinary request-pdf" href="/literature/literature-request/p594240" rel="nofollow" title="Request PDF of the Chemogenetics Research Bulletin">Request PDF<div class="lit_request_pdf"></div></a> </li> <li><a class="btn btn-quinary" href="/literature/research-bulletins" title="View all Research Bulletins">View all Research Bulletins</a></li> </ul> </div></div><div class="lit_item"> <div class="lit_content"> <div class="lit_image"> <a href="https://resources.tocris.com/images/literature/posters/fullsize/244891.jpg?v=1" data-toggle="lightbox" data-title="Alzheimer's Disease Poster" data-footer="<a href='/literature/literature-request/244891' rel='nofollow' title='Request copy of the Alzheimer's Disease'>Request copy</a> or <a class=' pdf-download' href='https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf' download='https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf' rel='nofollow' title='Download PDF of the Alzheimer's Disease' data-title='Alzheimer's Disease Poster'>Download PDF</a> today"><img loading="lazy" src="https://resources.tocris.com/images/literature/posters/regular/244891.jpg?v=1" alt="Alzheimer's Disease Poster" class="img-fluid"></a></div> <h4>Alzheimer's Disease Poster</h4> <p>Alzheimer's disease (AD) is a debilitating and progressive neurodegenerative disease and the most common cause of dementia, affecting approximately 30% of individuals aged over 85 years. This poster summarizes the cellular and molecular mechanisms of AD.</p> <ul class="pb_lit_buttons"><li> <a class="btn btn-quinary" href="/literature/literature-request/244891" rel="nofollow" title="Request copy of the Alzheimer's Disease Poster">Request copy</a> </li> <li><a class="btn btn-quinary pdf-download" href="https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf" download="https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf" rel="nofollow" target="_blank" title="Download PDF of the Alzheimer's Disease Poster" data-title="Alzheimer's Disease Poster">Download PDF<div class="lit_pdf"></div></a></li> <li><a class="btn btn-quinary" href="/literature/life-science-posters" title="View all Life Science Posters">View all Life Science Posters</a></li> </ul> </div></div><div class="lit_item"> <div class="lit_content"> <div class="lit_image"> <a href="https://resources.tocris.com/images/literature/posters/fullsize/234528.jpg" data-toggle="lightbox" data-title="Depression Poster" data-footer="<a href='/literature/literature-request/234528' rel='nofollow' title='Request copy of the Depression'>Request copy</a> or <a class=' pdf-download' href='https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf' download='https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf' rel='nofollow' title='Download PDF of the Depression' data-title='Depression Poster'>Download PDF</a> today"><img loading="lazy" src="https://resources.tocris.com/images/literature/posters/regular/234528.jpg" alt="Depression Poster" class="img-fluid"></a></div> <h4>Depression Poster</h4> <p>Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.</p> <ul class="pb_lit_buttons"><li> <a class="btn btn-quinary" href="/literature/literature-request/234528" rel="nofollow" title="Request copy of the Depression Poster">Request copy</a> </li> <li><a class="btn btn-quinary pdf-download" href="https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf" download="https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf" rel="nofollow" target="_blank" title="Download PDF of the Depression Poster" data-title="Depression Poster">Download PDF<div class="lit_pdf"></div></a></li> <li><a class="btn btn-quinary" href="/literature/life-science-posters" title="View all Life Science Posters">View all Life Science Posters</a></li> </ul> </div></div> </div> <div class="tab_content tab_5" data-tab="5"> </div> <div class="tab_content tab_6" data-tab="6"> </div> </div> </div> <div id="sidebar" class="col-xs-12 col-sm-4 col-md-3 col-lg-3 col-xl-3"> <div class="resources_sidebar_container"> <div class="fp_four_box"> <div class="fp_box_wrapper"><h3>Featured New Products</h3> <div class="fp_featured_product"><a href="/products/vu-0542270_8151">8151 | VU 0542270</a><br /> Selective inhibitor of K<sub>ir</sub>6.1 K<sub>ATP</sub> channels</div> <div class="fp_featured_product"><a href="/products/rna-imaging-probe-1c_8813">8813 | RNA Imaging Probe 1c</a><br /> Fluorogenic RNA imaging probe</div> <div class="fp_featured_product"><a href="/products/lsn-3318839_7959">7959 | LSN 3318839</a><br /> Glucagon-like peptide-1 receptor <br />(GLP1-R) positive allosteric modulator</div> <div class="fp_featured_product"><a href="/products/chir-99021-in-solution_8170">8170 | CHIR 99021 in solution</a><br /> Sterile-filtered 10 mM solution of CHIR 99021 pre-dissolved in DMSO</div> <div class="fp_featured_product"><a href="/products/bi-3231_8039">8039 | BI 3231</a><br /> Potent and selective hydroxysteroid 17尾 dehydrogenase 13 (HSD17B13) inhibitor</div> </div> </div> </div> <div class="distributor_region"></div> <div class="widget"> <div class="widget_title">Literature in this Area</div> <div class="widget_content carousel slide" id="ds_literature_scroller" data-ride="carousel" data-interval="8000">  <div class="carousel-inner"><div class="item active"><div class="highlight">Chemogenetics Research Bulletin</div> <a href="/literature/research-bulletins/chemogenetics"><img loading="lazy" src="https://resources.tocris.com/images/literature/research-bulletins/regular/594240.jpg?v=1" alt="Chemogenetics Research Bulletin"></a><p class="small">The chemogenetics research bulletin provides introduction to chemogenetic methods to manipulate neuronal activity.</p><a class="btn btn-quinary request-pdf" href="/literature/literature-request/p594240" rel="nofollow" title="Request PDF of the Chemogenetics Research Bulletin">Request PDF<div class="lit_request_pdf"></div></a></div><div class="item"><div class="highlight">Alzheimer's Life Science Poster</div><h5>Written by Dimitra Sokolova and Soyon Hong</h5> <a href="/literature/life-science-posters/alzheimers-disease"><img loading="lazy" src="https://resources.tocris.com/images/literature/posters/regular/244891.jpg?v=1" alt="Alzheimer's Disease Poster"></a><p class="small">Our Alzheimer's disease poster summarizes the genetic, molecular and cellular changes observed in the progression of this neurodegenerative disease.</p><a class="btn btn-quinary" href="/literature/literature-request/244891" rel="nofollow" title="Request copy of the Alzheimer's Disease Poster">Request copy</a><a class="btn btn-quinary pdf-download" href="https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf" download="https://resources.tocris.com/pdfs/literature/posters/alzheimers-poster-2023.pdf" rel="nofollow" target="_blank" title="Download PDF of the Alzheimer's Disease Poster" data-title="Alzheimer's Disease Poster">Download PDF<div class="lit_pdf"></div></a></div><div class="item"><div class="highlight">Depression Life Science Poster</div><h5>Written by P. Skolnich <em>et al</em></h5> <a href="/literature/life-science-posters/depression"><img loading="lazy" src="https://resources.tocris.com/images/literature/posters/regular/234528.jpg" alt="Depression Poster"></a><p class="small">Our Depression poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder.</p><a class="btn btn-quinary" href="/literature/literature-request/234528" rel="nofollow" title="Request copy of the Depression Poster">Request copy</a><a class="btn btn-quinary pdf-download" href="https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf" download="https://resources.tocris.com/pdfs/literature/posters/depression-poster-2015.pdf" rel="nofollow" target="_blank" title="Download PDF of the Depression Poster" data-title="Depression Poster">Download PDF<div class="lit_pdf"></div></a></div></div>  <a class="left carousel-control" href="#ds_literature_scroller" role="button" data-slide="prev"> <span 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