Organellular Imaging Reveals a Depletion of Endoplasmic Reticular Calcium During Post-ictal Cortical Spreading Depolarization

Overview

Journal bioRxiv

Date 2024 Oct 10

PMID 39386598

Authors

Matthew A Stern

Eric R Cole

Claire-Anne Gutekunst

Jenny J Yang

Ken Berglund

Robert E Gross

Affiliations

Soon will be listed here.

Abstract

During cortical spreading depolarization (CSD), neurons exhibit a dramatic increase in cytosolic calcium, which may be integral to CSD-mediated seizure termination. This calcium increase greatly exceeds that during seizures, suggesting the calcium source may not be solely extracellular. Thus, we sought to determine if the endoplasmic reticulum (ER), the largest intracellular calcium store, is involved. We developed a two-photon calcium imaging paradigm to simultaneously record the cytosol and ER during seizures in awake mice. Paired with direct current recording, we reveal that CSD can manifest as a slow post-ictal cytosolic calcium wave with a concomitant depletion of ER calcium that is spatiotemporally consistent with a calcium-induced calcium release. Importantly, we observed both naturally occurring and electrically induced CSD suppressed post-ictal epileptiform activity. Collectively, this work links ER dynamics to CSD, which serves as an innate process for seizure suppression and a potential mechanism underlying therapeutic electrical stimulation for epilepsy.

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