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Abstracts

Voltage Imaging Analysis of the Cellular and Network Mechanisms of Epileptic Biomarkers in Mice

Abstract number : 3.445
Submission category : 1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year : 2023
Submission ID : 1430
Source : www.aesnet.org
Presentation date : 12/4/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Mohammed Abumuaileq, BS – Biomedical Engineering Department, Boston University

Cara Ravasio, MS – Biomedical Engineering Department, Boston University; Athif Mohamed, MS – Biomedical Engineering Department, Boston University; Hua-an Tseng, PhD – Biomedical Engineering Department, Boston University; Wen Shi, PhD – Department of Neurology, Massachusetts General Hospital; Katherine Walsh, BS – Department of Neurology, Massachusetts General Hospital; Mark Kramer, PhD – Department of Mathematics and Statistics, Boston University; Catherine Chu, MD – Department of Neurology, Massachusetts General Hospital; Xue Han, PhD – Department of Biomedical Engineering, Boston University

Rationale: Memory dysfunction is the primary cognitive complaint of patients with mesial temporal lobe epilepsy. Hippocampal sharp wave ripples (SWRs) have been broadly linked to learning and memory, particularly during offline memory consolidation. Pathologic epileptic spikes and spikes combined with ripples (SR) impair memory. Each of these electrophysiological biomarkers reflect population-level electrical dynamics around the recording sites, and it is unclear how individual neurons within the local circuits relate to these electrophysiological features. Recently, we developed a fully genetically encoded voltage sensor, SomArchon, that allows precision analysis of membrane voltage from individual neurons, both action potentials and subthreshold voltage fluctuations, with sub-millisecond temporal resolution. This study aims to develop a rodent experimental platform that allows for temporally resolved analysis of cellular and network mechanisms of the physiological SWRs and the pathological spike and SR events. Specifically, we aim to develop SomArchon voltage imaging in the well-established intrahippocampal kainic acid mesial temporal epilepsy mouse models, which will permit the analysis of cellular membrane voltage during SWRs, spikes, and SRs.

Methods: Under stereotactic surgery, we injected kainic acid (100nL) into the hippocampus unilaterally, and then placed bipolar local field potential (LFP) recording electrodes in the CA1 and an imaging chamber over the CA1 stratum pyramidale. Status epilepticus was confirmed through behavioral observation immediately following kainic acid infusion and epilepsy confirmed with at least two subsequent spontaneous seizures observed behaviorally or on the LFP recording. LFP recordings in CA1 was performed in awake mice, and cellular voltage imaging from individual pyramidal cells was recorded by SomArchon fluorescence.

Results: We captured characteristic LFP events related to SWR, spikes, and SRs, including high-frequency ripples (Fig. 1A), large-deflection spikes (Fig. 1B), and simultaneous occurrence of the ripples and spikes (Fig. 1C), and the corresponding cellular membrane voltage activity of individual pyramidal cells.

Conclusions: We developed an experimental platform that enables the analysis of cellular membrane voltage of individual hippocampal CA1 neurons in a rodent model of temporal lobe epilepsy. This experimental platform allows the study of not only the action potentials of individual neurons but subthreshold membrane voltage fluctuations during both physiological LFP events related to memory consolidation (SWR) and pathologic LFP events linked to epilepsy and memory impairment (spikes and SRs).

Funding: NSF 2002971-DIOS
NIH 1R01NS119483
 


Basic Mechanisms