Activation of specific neuronal networks leads to different seizure onset types.
Title | Activation of specific neuronal networks leads to different seizure onset types. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Shiri Z, Manseau F, Lévesque M, Williams S, Avoli M |
Journal | Ann Neurol |
Volume | 79 |
Issue | 3 |
Pagination | 354-65 |
Date Published | 2016 Mar |
ISSN | 1531-8249 |
Abstract | OBJECTIVE: Ictal events occurring in temporal lobe epilepsy patients and in experimental models mimicking this neurological disorder can be classified, based on their onset pattern, into low-voltage, fast versus hypersynchronous onset seizures. It has been suggested that the low-voltage, fast onset pattern is mainly contributed by interneuronal (γ-aminobutyric acidergic) signaling, whereas the hypersynchronous onset involves the activation of principal (glutamatergic) cells.METHODS: Here, we tested this hypothesis using the optogenetic control of parvalbumin-positive or somatostatin-positive interneurons and of calmodulin-dependent, protein kinase-positive, principal cells in the mouse entorhinal cortex in the in vitro 4-aminopyridine model of epileptiform synchronization.RESULTS: We found that during 4-aminopyridine application, both spontaneous seizure-like events and those induced by optogenetic activation of interneurons displayed low-voltage, fast onset patterns that were associated with a higher occurrence of ripples than of fast ripples. In contrast, seizures induced by the optogenetic activation of principal cells had a hypersynchronous onset pattern with fast ripple rates that were higher than those of ripples.INTERPRETATION: Our results firmly establish that under a similar experimental condition (ie, bath application of 4-aminopyridine), the initiation of low-voltage, fast and of hypersynchronous onset seizures in the entorhinal cortex depends on the preponderant involvement of interneuronal and principal cell networks, respectively. |
DOI | 10.1002/ana.24570 |
Alternate Journal | Ann. Neurol. |
PubMed ID | 26605509 |
PubMed Central ID | PMC4878884 |
Grant List | 74609 / / Canadian Institutes of Health Research / Canada 8109 / / Canadian Institutes of Health Research / Canada MOP119340 / / Canadian Institutes of Health Research / Canada |