First Author | Shiri Z | Year | 2016 |
Journal | Ann Neurol | Volume | 79 |
Issue | 3 | Pages | 354-65 |
PubMed ID | 26605509 | Mgi Jnum | J:359670 |
Mgi Id | MGI:7788916 | Doi | 10.1002/ana.24570 |
Citation | Shiri Z, et al. (2016) Activation of specific neuronal networks leads to different seizure onset types. Ann Neurol 79(3):354-65 |
abstractText | 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 (gamma-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. |