Transitions between neocortical seizure and non-seizure-like states and their association with presynaptic glutamate release

Neurobiology of Disease

Yotin Chinvarun¹  Suzie Dufour²  Berj L. Bardakjian³  Peter L. Carlen⁴  Vanessa L. Breton⁵  Jose Martin Del Campo⁶ 

[1] Corresponding author at: 7KD-401, Krembil Research Institute, 60 Leonard Avenue Toronto, ON M5T 2S8, Canada.;Krembil Research Institute, Division of Fundamental Neurobiology, Toronto Western Hospital, Toronto, Ontario M5T 0S8, Canada;National Optics Institute, Biophotonics, Quebec, Canada G1P 4S4;Comprehensive Epilepsy Program and Neurology Unit, Phramongkutklao Hospital, Bangkok, Thailand;Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada;Krembil Research Institute, Division of Fundamental Neurobiology, Toronto Western Hospital, Toronto, Ontario M5T 0S8, Canada;

关键词: Seizure;    Electrophysiology;    Classification;    Prediction;    Neocortex;    Seizure-like events;   

DOI  :  

来源: DOAJ

【 摘 要 】

The transition between seizure and non-seizure states in neocortical epileptic networks is governed by distinct underlying dynamical processes. Based on the gamma distribution of seizure and inter-seizure durations, over time, seizures are highly likely to self-terminate; whereas, inter-seizure durations have a low chance of transitioning back into a seizure state. Yet, the chance of a state transition could be formed by multiple overlapping, unknown synaptic mechanisms. To identify the relationship between the underlying synaptic mechanisms and the chance of seizure-state transitions, we analyzed the skewed histograms of seizure durations in human intracranial EEG and seizure-like events (SLEs) in local field potential activity from mouse neocortical slices, using an objective method for seizure state classification. While seizures and SLE durations were demonstrated to have a unimodal distribution (gamma distribution shape parameter >1), suggesting a high likelihood of terminating, inter-SLE intervals were shown to have an asymptotic exponential distribution (gamma distribution shape parameter <1), suggesting lower probability of cessation. Then, to test cellular mechanisms for these distributions, we studied the modulation of synaptic neurotransmission during, and between, the in vitro SLEs. Using simultaneous local field potential and whole-cell voltage clamp recordings, we found a suppression of presynaptic glutamate release at SLE termination, as demonstrated by electrically- and optogenetically-evoked excitatory postsynaptic currents (EPSCs), and focal hypertonic sucrose application. Adenosine A1 receptor blockade interfered with the suppression of this release, changing the inter-SLE shape parameter from asymptotic exponential to unimodal, altering the chance of state transition occurrence with time. These findings reveal a critical role for presynaptic glutamate release in determining the chance of neocortical seizure state transitions.

【 授权许可】

Unknown