Cerebellar directed optogenetic intervention inhibits spontaneous hippocampal seizures in a mouse model of temporal lobe epilepsy

Esther Krook-Magnuson, Gergely G. Szabo, Caren Armstrong, Mikko Oijala, Ivan Soltesz

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Temporal lobe epilepsy is often medically refractory and new targets for intervention are needed. We used a mouse model of temporal lobe epilepsy, on-line seizure detection, and responsive optogenetic intervention to investigate the potential for cerebellar control of spontaneous temporal lobe seizures. Cerebellar targeted intervention inhibited spontaneous temporal lobe seizures during the chronic phase of the disorder. We further report that the direction of modulation as well as the location of intervention within the cerebellum can affect the outcome of intervention. Specifically, on-demand optogenetic excitation or inhibition of parvalbumin-expressing neurons, including Purkinje cells, in the lateral or midline cerebellum results in a decrease in seizure duration. In contrast, a consistent reduction in spontaneous seizure frequency occurs uniquely with on-demand optogenetic excitation of the midline cerebellum, and was not seen with intervention directly targeting the hippocampal formation. These findings demonstrate that the cerebellum is a powerful modulator of temporal lobe epilepsy, and that intervention targeting the cerebellum as a potential therapy for epilepsy should be revisited.

Original languageEnglish (US)
Article numbere.2014
JournaleNeuro
Volume1
Issue number1
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Keywords

  • Cerebellum
  • Epilepsy
  • Hippocampus
  • Optogenetics
  • Purkinje
  • Seizure

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