Optogenetic stimulus-triggered acquisition of seizure resistance

Yoshiteru Shimoda, Kaoru Beppu, Yoko Ikoma, Yosuke M. Morizawa, Satoshi Zuguchi, Utaro Hino, Ryutaro Yano, Yuki Sugiura, Satoru Moritoh, Yugo Fukazawa, Makoto Suematsu, Hajime Mushiake, Nobukazu Nakasato, Masaki Iwasaki, Kenji F. Tanaka, Teiji Tominaga, Ko Matsui

Research output: Contribution to journalArticlepeer-review

Abstract

Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such “kindling” process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed using in vivo microdialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.

Original languageEnglish
Article number105602
JournalNeurobiology of Disease
Volume163
DOIs
Publication statusPublished - 2022 Feb

Keywords

  • Adenosine
  • Anti-epileptic effect
  • Astrocyte
  • Epilepsy
  • Glia
  • Kindling
  • Optogenetics

ASJC Scopus subject areas

  • Neurology

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