| First Author | Yekhlef L | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 43230 | PubMed ID | 28230208 |
| Mgi Jnum | J:367283 | Mgi Id | MGI:8207557 |
| Doi | 10.1038/srep43230 | Citation | Yekhlef L, et al. (2017) Optogenetic activation of VGLUT2-expressing excitatory neurons blocks epileptic seizure-like activity in the mouse entorhinal cortex. Sci Rep 7:43230 |
| abstractText | We investigated whether an anti-epileptic effect is obtained by selectively activating excitatory neurons expressing ChR2 under the promoter for the synaptic vesicular glutamate transporter 2 (VGLUT2). VGLUT2-expressing cells were optically stimulated while local field potential and whole-cell patch-clamp recordings were performed in mouse entorhinal cortical slices perfused with the proconvulsive compound 4-aminopyridine (4-AP). In control conditions, blue light flashes directly depolarized the majority of putative glutamatergic cells, which in turn synaptically excited GABAergic interneurons. During bath perfusion with 4-AP, photostimuli triggered a fast EPSP-IPSP sequence which was often followed by tonic-clonic seizure-like activity closely resembling spontaneous ictal discharges. The GABA(A)-receptor antagonist gabazine blocked the progression of both light-induced and spontaneous seizures. Surprisingly, prolonged photostimuli delivered during ongoing seizures caused a robust interruption of synchronous discharges. Such break was correlated with a membrane potential depolarization block in principal cells, while putative GABAergic interneurons changed their firing activity from a burst-like to an irregular single-spike pattern. These data suggest that photostimulation of glutamatergic neurons triggers seizure-like activity only in the presence of an intact GABAergic transmission and that selectively activating the same glutamatergic cells robustly interrupts ongoing seizures by inducing a strong depolarization block, resulting in the disruption of paroxysmal burst-like firing. |
