Paradoxical effects of optogenetic stimulation in mesial temporal lobe epilepsy

Annals of Neurology
Maxime LévesqueMassimo Avoli

Abstract

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. 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. 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). Our findings show that the unilateral activation of CA3 PV-positive interneurons exerts anti-ictogenic effects associ...Continue Reading

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Citations

Apr 22, 2020·Epilepsy Currents·Esther Krook-Magnuson
Nov 10, 2020·PLoS Computational Biology·Elif Köksal ErsözFabrice Wendling
Jun 29, 2021·Revue neurologique·T Marissal
Jul 24, 2021·Cerebral Cortex Communications·Odile BartholomeBernard Rogister

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