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ABCDEF ... SUDEP: Action Potential Barrage in (Superior) Colliculus Causes( Spreading) Depolarization Leading to Epilepsy Fatality
Journal article   Open access   Peer reviewed

ABCDEF ... SUDEP: Action Potential Barrage in (Superior) Colliculus Causes( Spreading) Depolarization Leading to Epilepsy Fatality

Gordon F. Buchanan
Epilepsy currents, Vol.23(1), pp.53-55
01/2023
DOI: 10.1177/15357597221136962
PMCID: PMC10009128
PMID: 36923334
url
https://doi.org/10.1177/15357597221136962View
Published (Version of record) Open Access

Abstract

Cardiorespiratory arrest and death in mouse models of sudden unexpected death in epilepsy occur when spreading depolarization (SD) is triggered by cortical seizures and then propagates to the brainstem. However, the critical brain regions and the specific changes required to allow SD to propagate to the brainstem under the relatively rare circumstances leading to a fatal seizure are unknown. We previously found that following cortical seizure-inducing electrical stimulation, SD could occur in both the superior and inferior colliculi in Cacna1a(S218L) mice, but was never observed in wild-type animals or following non-seizure-inducing stimuli in Cacna1a(S218L) mice. Here, we show that optogenetic stimulation of the superior/inferior colliculi in Cacna1a(S218L) mice induces severe seizures, and resulting SD in the superior/inferior colliculi that propagates to the brainstem and correlates with the respiratory arrest followed by cardiac arrest. Further, we show that neurons of the superior colliculus in Cacna1a(S218L) mice exhibit hyperexcitable properties that we propose underlie a distinct susceptibility to SD. Our data suggest that the susceptibility of the superior colliculus to elicit fatal SD is a result of either genetic or seizure-related alterations within the superior colliculus that may involve changes to structure, connectivity and/or excitability.
Clinical Neurology Life Sciences & Biomedicine Neurosciences & Neurology Science & Technology

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