Optogenetic induction of hibernation-like state with modified human Opsin4 in mice

Tohru M. Takahashi, Arisa Hirano, Takeshi Kanda, Viviane M. Saito, Hiroto Ashitomi, Kazumasa Z. Tanaka, Yasufumi Yokoshiki, Kosaku Masuda, Masashi Yanagisawa, Kaspar E. Vogt, Takashi Tokuda, Takeshi Sakurai

Research output: Contribution to journalArticlepeer-review


We recently determined that the excitatory manipulation of Qrfp-expressing neurons in the preoptic area of the hypothalamus (quiescence-inducing neurons [Q neurons]) induced a hibernation-like hypothermic/hypometabolic state (QIH) in mice. To control the QIH with a higher time resolution, we develop an optogenetic method using modified human opsin4 (OPN4; also known as melanopsin), a G protein-coupled-receptor-type blue-light photoreceptor. C-terminally truncated OPN4 (OPN4dC) stably and reproducibly induces QIH for at least 24 h by illumination with low-power light (3 μW, 473 nm laser) with high temporal resolution. The high sensitivity of OPN4dC allows us to transcranially stimulate Q neurons with blue-light-emitting diodes and non-invasively induce the QIH. OPN4dC-mediated QIH recapitulates the kinetics of the physiological changes observed in natural hibernation, revealing that Q neurons concurrently contribute to thermoregulation and cardiovascular function. This optogenetic method may facilitate identification of the neural mechanisms underlying long-term dormancy states such as sleep, daily torpor, and hibernation.

Original languageEnglish (US)
Article number100336
JournalCell Reports Methods
Issue number11
StatePublished - Nov 21 2022
Externally publishedYes


  • GPCR
  • OPN4
  • QRFP
  • body temperature
  • fiber-less optogenetics
  • hibernation
  • melanopsin
  • neuroscience
  • optogenetics
  • torpor

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Genetics
  • Radiology Nuclear Medicine and imaging
  • Computer Science Applications


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