title: Dynamic, Cell-Type-Specific Roles for GABAergic Interneurons in a Mouse Model of Optogenetically Inducible Seizures.
abstract: GABAergic interneurons play critical roles in seizures, but it remains unknown whether these vary across interneuron subtypes or evolve during a seizure. This uncertainty stems from the unpredictable timing of seizures in most models, which limits neuronal imaging or manipulations around the seizure onset. Here, we describe a mouse model for optogenetic seizure induction. Combining this with calcium imaging, we find that seizure onset rapidly recruits parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptitde (VIP)-expressing interneurons, whereas excitatory neurons are recruited several seconds later. Optogenetically inhibiting VIP interneurons consistently increased seizure threshold and reduced seizure duration. Inhibiting PV+ and SOM+ interneurons had mixed effects on seizure initiation but consistently reduced seizure duration. Thus, while their roles may evolve during seizures, PV+ and SOM+ interneurons ultimately help maintain ongoing seizures. These results show how an optogenetically induced seizure model can be leveraged to pinpoint a new target for seizure control: VIP interneurons. VIDEO ABSTRACT.
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Sattar
authors.initials: S
authors.lastname: Khoshkhoo
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vogt
authors.affiliation: Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Weil Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA; Sloan Swartz Center for Theoretical Neurobiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA. Electronic address: vikaas.sohal@ucsf.edu.
authors.forename: Vikaas S
authors.initials: VS
authors.lastname: Sohal
mesh_terms: D000818:Animals; D000075402:Channelrhodopsins; D004195:Disease Models, Animal; D004569:Electroencephalography; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D009433:Neural Inhibition; D062308:Optogenetics / Q000379:methods*; D010320:Parvalbumins / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000503:physiopathology*; D013004:Somatostatin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D000075402:Channelrhodopsins; D010320:Parvalbumins; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin