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.


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


  • Channelrhodopsins
  • Parvalbumins
  • Vasoactive Intestinal Peptide
  • Somatostatin