Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation.

Journal Article (Journal Article)

It is well established that seizures beget seizures, yet the cellular processes that underlie progressive epileptogenesis remain unclear. Here, we use optogenetics to briefly activate targeted populations of mouse piriform cortex (PCx) principal neurons in vivo. After just 3 or 4 days of stimulation, previously subconvulsive stimuli trigger massive, generalized seizures. Highly recurrent allocortices are especially prone to "optokindling." Optokindling upsets the balance of recurrent excitation and feedback inhibition. To understand how this balance is disrupted, we then selectively reactivate the same neurons in vitro. Surprisingly, we find no evidence of heterosynaptic potentiation; instead, we observe a marked, pathway-specific decrease in feedback inhibition. We find no loss of inhibitory interneurons; rather, decreased GABA synthesis in feedback inhibitory neurons appears to underlie weakened inhibition. Optokindling will allow precise identification of the molecular processes by which brain activity patterns can progressively and pathologically disrupt the balance of cortical excitation and inhibition.

Full Text

Duke Authors

Cited Authors

  • Ryu, B; Nagappan, S; Santos-Valencia, F; Lee, P; Rodriguez, E; Lackie, M; Takatoh, J; Franks, KM

Published Date

  • April 20, 2021

Published In

Volume / Issue

  • 35 / 3

Start / End Page

  • 109001 -

PubMed ID

  • 33882304

Pubmed Central ID

  • PMC8102022

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2021.109001


  • eng

Conference Location

  • United States