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

doi:10.1016/j.crmeth.2022.100336

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

Cell Rep Methods. 2022 Nov 14;2(11):100336. doi: 10.1016/j.crmeth.2022.100336. eCollection 2022 Nov 21.

Authors

Tohru M Takahashi^{1

2}, Arisa Hirano^{1

2

3}, Takeshi Kanda², Viviane M Saito⁴, Hiroto Ashitomi⁴, Kazumasa Z Tanaka⁴, Yasufumi Yokoshiki⁵, Kosaku Masuda^{1

2}, Masashi Yanagisawa², Kaspar E Vogt², Takashi Tokuda^{3

5}, Takeshi Sakurai^{1

2}

Affiliations

¹ Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
² International Integrative Institute for Sleep medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan.
³ JST PRESTO, Japan.
⁴ Memory Research Unit, Okinawa Institute of Science and Technology Graduate University (OIST), Okinawa, Japan.
⁵ Institute of Innovative Research (IIR), Tokyo Institute of Technology, Tokyo, Japan.

Abstract

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.

Keywords: GPCR; OPN4; QRFP; body temperature; fiber-less optogenetics; hibernation; melanopsin; neuroscience; optogenetics; torpor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Hibernation* / physiology
Humans
Hypothalamus / physiology
Mice
Opsins* / genetics
Optogenetics
Sleep / physiology
Torpor* / physiology

Substances

Opsins