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

NEUROBIOLOGY OF DISEASE

卷:146

Article

Breton, Vanessa L.^1,3  Dufour, Suzie^3,4  Chinvarun, Yotin^7,8  Del Campo, Jose Martin⁶  Bardakjian, Berj L.^2,5  Carlen, Peter L.^1,3,6 

[1] Univ Toronto, Dept Physiol, Fac Med, Toronto, ON M5S 1A8, Canada

[2] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada

[3] Toronto Western Hosp, Krembil Res Inst, Div Fundamental Neurobiol, Toronto, ON M5T 0S8, Canada

[4] Biophotonics, Natl Opt Inst, Quebec City, PQ G1P 4S4, Canada

[5] Univ Toronto, Edward S Rogers Sr Dept Elect & Comp Engn, Toronto, ON M5S 3G4, Canada

[6] Univ Hlth Network, Dept Med Neurol, Toronto, ON M5G 2C4, Canada

[7] Phramongkutklao Hosp, Comprehens Epilepsy Program, Bangkok, Thailand

[8] Phramongkutklao Hosp, Neurol Unit, Bangkok, Thailand

关键词: Seizure;    Electrophysiology;    Classification;    Prediction;    Neocortex;    Seizure-like events;    Presynaptic;    Epilepsy;    Glutamate;    Adenosine;   

DOI  :  10.1016/j.nbd.2020.105124

来源: Elsevier

【 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 electricallyand 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.