{"doi":"10.1101/2021.06.30.450543","title":"Optogenetic stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsin variants yield opposite behavioral outcomes","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Optogenetic manipulation of genetically-specified neuron populations has become a key tool in circuit neuroscience. The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors; interestingly, this amygdalar structure contains a majority of GABAergic projection neurons. A previous study showed that optogenetic activation of MeA GABA neurons with channelrhodopsin-2\n                  <jats:sup>H134R</jats:sup>\n                  (ChR2) strongly enhanced inter-male aggression (Hong et al. 2014, Cell). When we attempted to reproduce these findings, accidentally using a faster channelrhodopsin variant (channelrhodopsin-2\n                  <jats:sup>H134R,E123T</jats:sup>\n                  or ChETA), we found the opposite results. We therefore systematically compared the behavioral outcome of optogenetic stimulation of MeApd GABA neurons with ChETA versus ChR2, employing two widely used AAV serotypes. This revealed that optogenetic stimulation with ChETA\n                  <jats:italic>suppressed</jats:italic>\n                  aggression, whereas optogenetic stimulation with ChR2\n                  <jats:italic>increased</jats:italic>\n                  aggression. Recordings of membrane potential changes following optogenetic stimulation with ChETA versus ChR2 revealed larger plateau depolarizations, smaller action potential amplitudes, and larger local inhibition of neighboring inhibitory neurons with ChR2 as compared to ChETA. Our study shows that channelrhodopsin variants have to be chosen with care for\n                  <jats:italic>in-vivo</jats:italic>\n                  optogenetic experiments. Furthermore, the role of MeApd GABA neurons in aggression control should be re- evaluated.\n                </jats:p>","journal":null,"year":null,"id":598367,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1533196,"name":"Ralf Schneggenburger","orcid":"0000-0002-6223-2830","position":1,"is_corresponding":false},{"id":1533197,"name":"Olexiy Kochubey","orcid":"0000-0002-8115-7733","position":2,"is_corresponding":false},{"id":628942,"name":"Aiste Baleisyte","orcid":"0000-0003-3532-1368","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Optogenetic stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsin variants yield opposite behavioral outcomes","abstract":"<jats:title>Summary</jats:title>\n                <jats:p>\n                  Optogenetic manipulation of genetically-specified neuron populations has become a key tool in circuit neuroscience. The medial amygdala (MeA) receives pheromone information about conspecifics and has crucial functions in social behaviors; interestingly, this amygdalar structure contains a majority of GABAergic projection neurons. A previous study showed that optogenetic activation of MeA GABA neurons with channelrhodopsin-2\n                  <jats:sup>H134R</jats:sup>\n                  (ChR2) strongly enhanced inter-male aggression (Hong et al. 2014, Cell). When we attempted to reproduce these findings, accidentally using a faster channelrhodopsin variant (channelrhodopsin-2\n                  <jats:sup>H134R,E123T</jats:sup>\n                  or ChETA), we found the opposite results. We therefore systematically compared the behavioral outcome of optogenetic stimulation of MeApd GABA neurons with ChETA versus ChR2, employing two widely used AAV serotypes. This revealed that optogenetic stimulation with ChETA\n                  <jats:italic>suppressed</jats:italic>\n                  aggression, whereas optogenetic stimulation with ChR2\n                  <jats:italic>increased</jats:italic>\n                  aggression. Recordings of membrane potential changes following optogenetic stimulation with ChETA versus ChR2 revealed larger plateau depolarizations, smaller action potential amplitudes, and larger local inhibition of neighboring inhibitory neurons with ChR2 as compared to ChETA. Our study shows that channelrhodopsin variants have to be chosen with care for\n                  <jats:italic>in-vivo</jats:italic>\n                  optogenetic experiments. Furthermore, the role of MeApd GABA neurons in aggression control should be re- evaluated.\n                </jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21097893","pmcid":null,"openalex_id":"https://openalex.org/W3174750407","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2021,"count":1},{"year":2022,"count":1}],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/06/30/2021.06.30.450543.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/06/30/2021.06.30.450543.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.06.30.450543","host_type":"publisher"},{"url":"https://doi.org/10.1101/2021.06.30.450543","host_type":"repository"}],"fields_of_study":["Photoreceptor and optogenetics research","Neuroscience and Neuropharmacology Research","Nicotinic Acetylcholine Receptors Study"],"mesh_terms":[],"keywords":["Optogenetics","Channelrhodopsin","Neuroscience","Stimulation","Amygdala","GABAergic","Inhibitory postsynaptic potential","Psychology","Biology"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.5281/zenodo.4311846","title":"Stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsins yields opposite behavioral outcomes","publisher":"Zenodo","resource_type":"Dataset"},{"doi":"10.5281/zenodo.4311847","title":"Stimulation of medial amygdala GABA neurons with kinetically different channelrhodopsins yields opposite behavioral outcomes","publisher":"Zenodo","resource_type":"Dataset"}],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T15:34:53.215210Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}