title: Action potential initiation in neocortical inhibitory interneurons.
abstract: Action potential (AP) generation in inhibitory interneurons is critical for cortical excitation-inhibition balance and information processing. However, it remains unclear what determines AP initiation in different interneurons. We focused on two predominant interneuron types in neocortex: parvalbumin (PV)- and somatostatin (SST)-expressing neurons. Patch-clamp recording from mouse prefrontal cortical slices showed that axonal but not somatic Na+ channels exhibit different voltage-dependent properties. The minimal activation voltage of axonal channels in SST was substantially higher (∼7 mV) than in PV cells, consistent with differences in AP thresholds. A more mixed distribution of high- and low-threshold channel subtypes at the axon initial segment (AIS) of SST cells may lead to these differences. Surprisingly, NaV1.2 was found accumulated at AIS of SST but not PV cells; reducing NaV1.2-mediated currents in interneurons promoted recurrent network activity. Together, our results reveal the molecular identity of axonal Na+ channels in interneurons and their contribution to AP generation and regulation of network activity.
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Tun
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Tian
authors.affiliation: U.O. of Neurophysiopathology and Diagnostic Epileptology, Foundation Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Neurological Institute Carlo Besta, Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Scalmani
authors.affiliation: U.O. of Clinical Epileptology and Experimental Neurophysiology, Foundation Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Neurological Institute Carlo Besta, Milano, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Frassoni
authors.affiliation: Institute of Molecular and Cellular Pharmacology (IPMC), Laboratory of Excellence Ion Channel Science and Therapeutics (LabEx ICST), CNRS UMR7275 and University of Nice-Sophia Antipolis, Valbonne, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mantegazza
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mingpo
authors.initials: M
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, School of Brain and Cognitive Sciences, Beijing Normal University, Beijing, China; Center for Collaboration and Innovation in Brain and Learning Sciences, Beijing Normal University, Beijing, China.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000378:metabolism; D015870:Gene Expression; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008867:Microtomy; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D010320:Parvalbumins; D013004:Somatostatin