{"doi":"10.1523/jneurosci.3482-15.2016","title":"An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons","abstract":"<jats:p>To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2–P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2–P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9–P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animals<jats:italic>in vivo</jats:italic>, we found that photostimulation of interneurons reduces EPSC frequency at ages P3–P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices<jats:italic>in vitro</jats:italic>, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex<jats:italic>in vivo</jats:italic>.</jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT</jats:bold>We report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pups<jats:italic>in vitro</jats:italic>, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampus<jats:italic>in vivo</jats:italic>.</jats:p>","journal":"The Journal of Neuroscience","year":2016,"id":663696,"datarank":0.7242470605953454,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"self_citation_contribution":0.7242470605953454,"citation_network_contribution":0.0,"self_endowment_contribution":0.7242470605953454,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":124,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":1732877,"name":"Thomas Tressard","orcid":null,"position":1,"is_corresponding":false},{"id":1732878,"name":"Marat Mukhtarov","orcid":null,"position":2,"is_corresponding":false},{"id":1732879,"name":"Agnes Baude","orcid":null,"position":3,"is_corresponding":false},{"id":1732880,"name":"Rustem Khazipov","orcid":null,"position":4,"is_corresponding":false},{"id":1732876,"name":"Guzel Valeeva","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons","abstract":"<jats:p>To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2–P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2–P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9–P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animals<jats:italic>in vivo</jats:italic>, we found that photostimulation of interneurons reduces EPSC frequency at ages P3–P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slices<jats:italic>in vitro</jats:italic>, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortex<jats:italic>in vivo</jats:italic>.</jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT</jats:bold>We report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pups<jats:italic>in vitro</jats:italic>, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampus<jats:italic>in vivo</jats:italic>.</jats:p>","is_dataset_classified":null,"base_score":4.8283137373023015,"endowment":4.8283137373023015,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27251618","pmcid":"PMC6601813","openalex_id":"https://openalex.org/W2417336554","authors":[],"funders":[],"total_grants":0,"fwci":8.041,"citation_percentile":0.98365301,"influential_citations":0,"citation_trend":[{"year":2016,"count":4},{"year":2017,"count":21},{"year":2018,"count":7},{"year":2019,"count":20},{"year":2020,"count":16},{"year":2021,"count":21},{"year":2022,"count":15},{"year":2023,"count":6},{"year":2024,"count":5},{"year":2025,"count":8},{"year":2026,"count":1}],"oa_status":"bronze","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","oa_locations":[{"url":"https://www.jneurosci.org/content/jneuro/36/22/5961.full.pdf","host_type":"journal"},{"url":"https://www.jneurosci.org/content/jneuro/36/22/5961.full.pdf","host_type":"publisher"},{"url":"https://syndication.highwire.org/content/doi/10.1523/JNEUROSCI.3482-15.2016","host_type":"publisher"},{"url":"https://doi.org/10.1523/jneurosci.3482-15.2016","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27251618","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6601813","host_type":"repository"}],"fields_of_study":["Photoreceptor and optogenetics research","Neuroscience and Neuropharmacology Research","Neuroendocrine regulation and behavior","Age Factors","Animals","Animals, Newborn","Channelrhodopsins","Excitatory Amino Acid Agents","GABA Agents","GABAergic Neurons","Gene Expression Regulation, Developmental","Glutamate Decarboxylase","Glutamic Acid","Hippocampus","In Vitro Techniques","Inhibitory Postsynaptic Potentials","Mice","Mice, Transgenic","Neocortex","Neural Inhibition","Optogenetics","Patch-Clamp Techniques","Synaptic Potentials","gamma-Aminobutyric Acid"],"mesh_terms":["Channelrhodopsins","Age Factors","Animals","Animals, Newborn","gamma-Aminobutyric Acid","Glutamate Decarboxylase","Hippocampus","Mice, Transgenic","Neural Inhibition","Patch-Clamp Techniques","Gene Expression Regulation, Developmental","GABA Agents","Excitatory Amino Acid Agents","Glutamic Acid","Neocortex","Mice","Inhibitory Postsynaptic Potentials","Synaptic Potentials","GABAergic Neurons","Optogenetics","In Vitro Techniques"],"keywords":["Photostimulation","Excitatory postsynaptic potential","Inhibitory postsynaptic potential","Neuroscience","GABAergic","Optogenetics","Glutamatergic","Channelrhodopsin","Hippocampal formation","Biology","Glutamate receptor","Cortex","Hippocampus","Inhibition","Patch clamp","GABA","Interneurons","Chr2"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T23:09:07.871042Z","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":[]}