[ONOS Seminar Series] Professor Takeshi Sakurai: Induction of hibernation-like state in mice

OIST Neuroscience Club is excited to host Prof. Takeshi Sakurai from the International Institute for Integrative Sleep (WPI-IIIS) Medicine, University of Tsukuba. Everyone is welcome to join the seminar!

Induction of hibernation-like state in mice

Prof. Takeshi Sakurai

Faculty of Medicine/WPI-IIIS, University of Tsukuba

Hibernation serves as a biological strategy for thermoregulatory mammals to adapt to harsh environments, typically described as a regulated, hypothermic, and hypometabolic state that persists for an extended period. Recent research has identified a neuronal population that induces a hibernation-like hypometabolic state in mice and rats, which do not typically hibernate. These neurons, known as quiescence-inducing neurons (Q neurons), express a gene encoding the neuropeptide pyroglutamylated RFamide peptide (QRFP) and are located in the anteroventral periventricular nucleus (AVPe) within the preoptic area (POA) of the hypothalamus. The induced state, referred to as the Q-neuron-induced hypothermic/hypometabolic state (QIH), is similar to hibernation, including a resetting of the body temperature set-point. Induction of QIH was achieved through the use of chemogenetics, specifically utilizing the hM3Dq designer receptor exclusively activated by the designer drug (DREADD) system. The core body temperature (TB) and metabolic rate of mice decreased immediately following administration of clozapine-N-oxide (CNO), and recovery from DREADD-mediated QIH was slow, requiring several days. The slow recovery process, however, hinders examination of the effects of QIH-related hypometabolism on various physiological processes, obscuring the effects of QIH on these functions.

Recently, we have developed a method utilizing optogenetics with a modified OPN4, which is useful for inducing and maintaining long-term (up to 24 hours) QIH with rapid recovery in mice, mimicking hibernation. Activation of C-terminally truncated OPN4 (OPN4dC) with low-power light allows for induction of QIH with very low light intensity, even enabling noninvasive transcranial stimulation with blue light-emitting diodes (LEDs). This study demonstrates that GPCR-type optogenetic manipulation of neurons is a powerful technique for examining neural function in slow and sustained physiological processes (hours to one day) with high spatiotemporal resolution.

You can join the seminar via ZOOM (meeting ID: 97850326939).