Non-invasive optical control of endogenous Ca 2+ channels in awake mice

Nat Commun. 2020 Jan 10;11(1):210. doi: 10.1038/s41467-019-14005-4.

Abstract

Optogenetic approaches for controlling Ca2+ channels provide powerful means for modulating diverse Ca2+-specific biological events in space and time. However, blue light-responsive photoreceptors are, in principle, considered inadequate for deep tissue stimulation unless accompanied by optic fiber insertion. Here, we present an ultra-light-sensitive optogenetic Ca2+ modulator, named monSTIM1 encompassing engineered cryptochrome2 for manipulating Ca2+ signaling in the brain of awake mice through non-invasive light delivery. Activation of monSTIM1 in either excitatory neurons or astrocytes of mice brain is able to induce Ca2+-dependent gene expression without any mechanical damage in the brain. Furthermore, we demonstrate that non-invasive Ca2+ modulation in neurons can be sufficiently and effectively translated into changes in behavioral phenotypes of awake mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes
  • Brain / metabolism
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Cryptochromes / chemistry
  • Cryptochromes / genetics
  • Cryptochromes / metabolism*
  • Fiber Optic Technology*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Mice
  • Neurons / metabolism
  • Optogenetics*
  • Sequence Alignment
  • Stromal Interaction Molecule 1 / chemistry
  • Stromal Interaction Molecule 1 / metabolism*
  • Wakefulness

Substances

  • Calcium Channels
  • Cry2 protein, mouse
  • Cryptochromes
  • Stim1 protein, mouse
  • Stromal Interaction Molecule 1
  • Calcium