Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks

Nat Commun. 2021 Jul 23;12(1):4488. doi: 10.1038/s41467-021-24718-0.

Abstract

Opn7b is a non-visual G protein-coupled receptor expressed in zebrafish. Here we find that Opn7b expressed in HEK cells constitutively activates the Gi/o pathway and illumination with blue/green light inactivates G protein-coupled inwardly rectifying potassium channels. This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light. Consistent with this prediction, illumination of recombinant expressed Opn7b in cortical pyramidal cells results in increased neuronal activity. In awake mice, light stimulation of Opn7b expressed in pyramidal cells of somatosensory cortex reliably induces generalized epileptiform activity within a short (<10 s) delay after onset of stimulation. Our study demonstrates a reversed mechanism for G protein-coupled receptor control and Opn7b as a tool for controlling neural circuit properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism*
  • Neurons / physiology
  • Opsins / genetics
  • Opsins / metabolism*
  • Optogenetics / methods*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / genetics
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / metabolism
  • Synapses / genetics
  • Synapses / physiology
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Opsins
  • Receptors, G-Protein-Coupled
  • Zebrafish Proteins
  • GTP-Binding Proteins