Abstract | 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 γ- aminobutyric acid type A signaling can also initiate ictogenesis. ANN NEUROL 2019;86:714-728.
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Authors | Maxime Lévesque, Li-Yuan Chen, Guillaume Etter, Zahra Shiri, Siyan Wang, Sylvain Williams, Massimo Avoli |
Journal | Annals of neurology
(Ann Neurol)
Vol. 86
Issue 5
Pg. 714-728
(11 2019)
ISSN: 1531-8249 [Electronic] United States |
PMID | 31393618
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2019 American Neurological Association. |
Chemical References |
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Topics |
- Animals
- CA3 Region, Hippocampal
(physiopathology)
- Convulsants
(toxicity)
- Epilepsy, Temporal Lobe
(chemically induced, physiopathology)
- Interneurons
(physiology)
- Male
- Mice
- Mice, Transgenic
- Optogenetics
- Pilocarpine
(toxicity)
- Seizures
(chemically induced, physiopathology)
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