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

Sattar Khoshkhoo; Daniel Vogt; Vikaas S Sohal

doi:10.1016/j.neuron.2016.11.043

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

Neuron. 2017 Jan 18;93(2):291-298. doi: 10.1016/j.neuron.2016.11.043. Epub 2016 Dec 29.

Authors

Sattar Khoshkhoo¹, Daniel Vogt², Vikaas S Sohal³

Affiliations

¹ 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.
² 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.
³ 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.

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.

Publication types

Video-Audio Media

MeSH terms

Animals
Channelrhodopsins
Disease Models, Animal*
Electroencephalography
GABAergic Neurons / metabolism
GABAergic Neurons / physiology*
Interneurons / metabolism
Interneurons / physiology*
Mice*
Motor Cortex / metabolism
Motor Cortex / physiopathology*
Neural Inhibition*
Optogenetics / methods*
Parvalbumins / metabolism
Seizures / metabolism
Seizures / physiopathology*
Somatostatin / metabolism
Vasoactive Intestinal Peptide / metabolism

Substances

Channelrhodopsins
Parvalbumins
Vasoactive Intestinal Peptide
Somatostatin

Abstract

Publication types

MeSH terms

Substances

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