Optogenetic control of motor coordination by Gi/o protein-coupled vertebrate rhodopsin in cerebellar Purkinje cells

J Biol Chem. 2011 Jul 22;286(29):25848-58. doi: 10.1074/jbc.M111.253674. Epub 2011 May 31.

Abstract

G protein-coupled receptors are involved in the modulation of complex neuronal networks in the brain. To investigate the impact of a cell-specific G(i/o) protein-mediated signaling pathway on brain function, we created a new optogenetic mouse model in which the G(i/o) protein-coupled receptor vertebrate rhodopsin can be cell-specifically expressed with the aid of Cre recombinase. Here we use this mouse model to study the functional impact of G(i/o) modulation in cerebellar Purkinje cells (PCs). We show that in vivo light activation of vertebrate rhodopsin specifically expressed in PCs reduces simple spike firing that is comparable with the reduction in firing observed for the activation of cerebellar G(i/o)-coupled GABA(B) receptors. Notably, the light exposure of the cerebellar vermis in freely moving mice changes the motor behavior. Thus, our studies directly demonstrate that spike modulation via G(i/o)-mediated signaling in cerebellar PCs affects motor coordination and show a new promising approach for studying the physiological function of G protein-coupled receptor-mediated signaling in a cell type-specific manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / radiation effects
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism*
  • Gene Expression Regulation / radiation effects
  • Light
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity / genetics*
  • Motor Activity / radiation effects*
  • Optical Phenomena*
  • Purkinje Cells / metabolism*
  • Purkinje Cells / radiation effects*
  • Rhodopsin / genetics
  • Rhodopsin / metabolism*
  • Signal Transduction / radiation effects

Substances

  • Rhodopsin
  • GTP-Binding Protein alpha Subunits, Gi-Go