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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.

SUBMITTER: Khoshkhoo S 

PROVIDER: S-EPMC5268075 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Dynamic, Cell-Type-Specific Roles for GABAergic Interneurons in a Mouse Model of Optogenetically Inducible Seizures.

Khoshkhoo Sattar S   Vogt Daniel D   Sohal Vikaas S VS  

Neuron 20161229 2


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 va  ...[more]

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