title: Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.
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.
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Moran
authors.initials: M
authors.lastname: Furman
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.|Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Cian
authors.initials: C
authors.lastname: McCafferty
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Lerner
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Motelow
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Chanthia
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Buchanan
authors.affiliation: Psychology, Princeton University, Princeton, New Jersey, U.S.A.
authors.forename: Ilana B
authors.initials: IB
authors.lastname: Witten
authors.affiliation: Bioengineering, Psychiatry and Behavioral Science, Stanford University, Stanford, California, U.S.A.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, U.S.A.|Kavli Institute, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cardin
authors.affiliation: Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, U.S.A.|Department of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, U.S.A.|Kavli Institute, Yale University School of Medicine, New Haven, Connecticut, U.S.A.|Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, U.S.A.
authors.forename: Hal
authors.initials: H
authors.lastname: Blumenfeld
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology*; D000075402:Channelrhodopsins; D059329:Cholinergic Neurons / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D065726:Limbic Lobe / Q000503:physiopathology*; D008297:Male; D062308:Optogenetics / Q000379:methods*; D045042:Pedunculopontine Tegmental Nucleus / Q000503:physiopathology; D010775:Photic Stimulation; D051381:Rats; D020318:Rats, Long-Evans; D012640:Seizures / Q000503:physiopathology*
chemical_list: D000075402:Channelrhodopsins
keywords: Acetylcholine; Consciousness; Epilepsy; Neurostimulation; Optogenetics; Sudden unexpected death in epilepsy (SUDEP)