Authors

Brendan Ryu,1 Shivathmihai Nagappan,1 Fernando Santos-Valencia,1 Psyche Lee,1 Erica Rodriguez,1 Meredith Lackie,1 Jun Takatoh,1 and Kevin M. Franks1,2,*

Affiliations

1Department of Neurobiology, Duke University Medical School, Durham, NC 27705, USA

Topic

Neuroscience, Optogenetics

Abstract

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.

DOI: https://dx.doi.org/10.1016%2Fj.celrep.2021.109001

Extract

We recorded in voltage-clamp from uninfected cells adjacent to the infection site. To ensure cells were uninfected we first examined responses to weak, 1 s long light pulses (470 nm, CoolLED) delivered through the 40x objective.

Product Associated Features

The compact, single-bandwidth pE-100 is ideal for optogenetic stimulation with the ability to perform precise pulsing at different durations.

Product Type

-

Journal

Cell Reports

Year of Publication

2021

Country of Publication

USA