Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation

Takuya Sasaki, Kaoru Beppu, Kenji F. Tanaka, Yugo Fukazawa, Ryuichi Shigemoto, Ko Matsui

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

Dynamic activity of glia has repeatedly been demonstrated, but if such activity is independent from neuronal activity, glia would not have any role in the information processing in the brain or in the generation of animal behavior. Evidence for neurons communicating with glia is solid, but the signaling pathway leading back from glial-to-neuronal activity was often difficult to study. Here, we introduced a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel, was expressed in astrocytes. Selective photostimulation of these astrocytes in vivo triggered neuronal activation. Using slice preparations, we show that glial photostimulation leads to release of glutamate, which was sufficient to activate AMPA receptors on Purkinje cells and to induce long-term depression of parallel fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors. In contrast to neuronal synaptic vesicular release, glial activation likely causes preferential activation of extrasynaptic receptors that appose glial membrane. Finally, we show that neuronal activation by glial stimulation can lead to perturbation of cerebellar modulated motor behavior. These findings demonstrate that glia can modulate the tone of neuronal activity and behavior. This animal model is expected to be a potentially powerful approach to study the role of glia in brain function.

Original languageEnglish
Pages (from-to)20720-20725
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number50
DOIs
Publication statusPublished - 2012 Dec 11

Keywords

  • Bergmann glia
  • C-fos
  • Cerebellum
  • Gliotransmitter
  • Plasticity

ASJC Scopus subject areas

  • General

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