| Autor: |
Merricks EM, Deshpande SS, Agopyan-Miu AH, Smith EH, Schlafly ED, McKhann GM, Goodman RR, Sheth SA, Greger B, House PA, Eskandar EN, Madsen JR, Cash SS, Trevelyan AJ, van Drongelen W, Schevon CA |
| Jazyk: |
angličtina |
| Zdroj: |
MedRxiv : the preprint server for health sciences [medRxiv] 2024 Jan 26. Date of Electronic Publication: 2024 Jan 26. |
| DOI: |
10.1101/2024.01.26.24301821 |
| Abstrakt: |
There is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose that transient blocking of inhibitory firing due to selective fast-spiking interneuron saturation-resulting from intense excitatory synaptic drive-is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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