Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology

Moran Furman; Qiong Zhan; Cian McCafferty; Benjamin A Lerner; Joshua E Motelow; Jin Meng; Chanthia Ma; Gordon F Buchanan; Ilana B Witten; Karl Deisseroth; Jessica A Cardin; Hal Blumenfeld

doi:10.1111/epi.13220

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Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology

Journal article

Open access

Peer reviewed

Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology

Moran Furman, Qiong Zhan, Cian McCafferty, Benjamin A Lerner, Joshua E Motelow, Jin Meng, Chanthia Ma, Gordon F Buchanan, Ilana B Witten, Karl Deisseroth, …

Epilepsia (Copenhagen), Vol.56(12), pp.e198-e202

12/2015

DOI: 10.1111/epi.13220

PMCID: PMC4679683

PMID: 26530287

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Abstract

Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.

Optogenetics - methods

Pedunculopontine Tegmental Nucleus - physiopathology

Rats, Long-Evans

Channelrhodopsins

Rats

Male

Limbic Lobe - physiopathology

Cerebral Cortex - physiopathology

Cholinergic Neurons - physiology

Seizures - physiopathology

Animals

Female

Brain Stem - physiopathology

Photic Stimulation

Disease Models, Animal

Details

Title: Subtitle: Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology
Creators: Moran Furman - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Qiong Zhan - Xiangya Hospital, Central South University, Changsha, China
Cian McCafferty - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Benjamin A Lerner - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Joshua E Motelow - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Jin Meng - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Chanthia Ma - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Gordon F Buchanan - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Ilana B Witten - Psychology, Princeton University, Princeton, New Jersey, U.S.A
Karl Deisseroth - Bioengineering, Psychiatry and Behavioral Science, Stanford University, Stanford, California, U.S.A
Jessica A Cardin - Kavli Institute, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Hal Blumenfeld - Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A
Resource Type: Journal article
Publication Details: Epilepsia (Copenhagen), Vol.56(12), pp.e198-e202
DOI: 10.1111/epi.13220
PMID: 26530287
PMCID: PMC4679683
NLM abbreviation: Epilepsia
ISSN: 0013-9580
eISSN: 1528-1167
Publisher: United States
Grant note: R01 EY022951 / NEI NIH HHS R21 NS083783 / NINDS NIH HHS R01 NS066974 / NINDS NIH HHS R01 MH102365 / NIMH NIH HHS P30 NS052519 / NINDS NIH HHS T32 GM007205 / NIGMS NIH HHS
Language: English
Date published: 12/2015
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020601802771

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