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

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 journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Article number	100336
Journal	Cell Reports Methods
Volume	2
Issue number	11
DOIs	https://doi.org/10.1016/j.crmeth.2022.100336
State	Published - Nov 21 2022
Externally published	Yes

Keywords

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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10.1016/j.crmeth.2022.100336

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title = "Optogenetic induction of hibernation-like state with modified human Opsin4 in mice",

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",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = nov,

day = "21",

doi = "10.1016/j.crmeth.2022.100336",

language = "English (US)",

volume = "2",

journal = "Cell Reports Methods",

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TY - JOUR

T1 - Optogenetic induction of hibernation-like state with modified human Opsin4 in mice

AU - Takahashi, Tohru M.

AU - Hirano, Arisa

AU - Kanda, Takeshi

AU - Saito, Viviane M.

AU - Ashitomi, Hiroto

AU - Tanaka, Kazumasa Z.

AU - Yokoshiki, Yasufumi

AU - Masuda, Kosaku

AU - Yanagisawa, Masashi

AU - Vogt, Kaspar E.

AU - Tokuda, Takashi

AU - Sakurai, Takeshi

PY - 2022/11/21

Y1 - 2022/11/21

N2 - 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.

AB - 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.

KW - GPCR

KW - OPN4

KW - QRFP

KW - body temperature

KW - fiber-less optogenetics

KW - hibernation

KW - melanopsin

KW - neuroscience

KW - optogenetics

KW - torpor

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DO - 10.1016/j.crmeth.2022.100336

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SN - 2667-2375

VL - 2

JO - Cell Reports Methods

JF - Cell Reports Methods

IS - 11

M1 - 100336

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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