| First Author | Lévesque M | Year | 2019 |
| Journal | Ann Neurol | Volume | 86 |
| Issue | 5 | Pages | 714-728 |
| PubMed ID | 31393618 | Mgi Jnum | J:348016 |
| Mgi Id | MGI:7627215 | Doi | 10.1002/ana.25572 |
| Citation | Levesque M, et al. (2019) Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy. Ann Neurol 86(5):714-728 |
| abstractText | OBJECTIVE: To establish the effects induced by long-term, unilateral stimulation of parvalbumin (PV)-positive interneurons on seizures, interictal spikes, and high-frequency oscillations (80-500Hz) occurring after pilocarpine-induced status epilepticus (SE)-a proven model of mesial temporal lobe epilepsy (MTLE)-in transgenic mice expressing or not expressing ChR2. METHODS: PV-ChR2 (n = 6) and PV-Cre (n = 6) mice were treated with pilocarpine to induce SE. Three hours after SE onset, unilateral optogenetic stimulation (450nm, 25mW, 20-millisecond pulses delivered at 8Hz for 30 seconds every 2 minutes) of CA3 PV-positive interneurons was implemented for 14 continuous days in both groups. RESULTS: Rates of seizures (p < 0.01), interictal spikes (p < 0.001), and interictal spikes with fast ripples (250-500Hz) (p < 0.001) were lower in PV-ChR2 than in PV-Cre mice. Ripples (80-200Hz) occurring outside of interictal spikes had higher rates in the PV-ChR2 group (p < 0.01), whereas isolated fast ripples had lower rates (p < 0.01). However, seizure probability was higher during optogenetic stimulation in PV-ChR2 compared to PV-Cre animals (p < 0.05). INTERPRETATION: Our findings show that the unilateral activation of CA3 PV-positive interneurons exerts anti-ictogenic effects associated with decreased rates of interictal spikes and fast ripples in this MTLE model. However, PV-positive interneuron stimulation can paradoxically trigger seizures in epileptic animals, supporting the notion that gamma-aminobutyric acid type A signaling can also initiate ictogenesis. ANN NEUROL 2019;86:714-728. |
