Nature. A neural circuit that causes a hibernating state.

In order to maintain body temperature, the body temperature is generally higher than the ambient temperature.however, some mammals can take the initiative to lower their body temperature, store energy in hibernation state, and survive the food shortage in winter [1].laboratory mice did not hibernate, but showed a short-term (less than 24 h) low metabolism state, known as daily torpor [2], during which reducing basic metabolism is beneficial to the health of the body.some experiments have confirmed that both hibernation and hibernation are regulated by the central nervous system [3], but the mechanism is still unclear.artificial induction of hibernation like hypometabolism in non hibernating animals, including humans, will contribute to the development of many medical applications and the realization of remote space exploration in the future.recently, a team of genshiro a. Sunagawa from Takeshi samurai of Tsukuba University of Japan and RIKEN biological system dynamics research center of Japan published the title of a discrete neural circuit induces a hibernation like state in nature Rodents article, found that rodent hypothalamic neural circuit can lead to hibernation like long-term hypothermia and hypometabolism state.in this state, although body temperature and oxygen consumption are kept at very low levels, the ability to regulate metabolism remains as normal as hibernation.after recovering from this state, there was no obvious damage or abnormal behavior of tissues and organs.the mRNA of hypothalamic neuropeptide qrfp was localized in the hypothalamus, and distributed in the lateral hypothalamic area (LHA), tubercle (tubercle) and periventricular nucleus (periventricular nucleus).qrfp was associated with food intake, sympathetic regulation and anxiety.the researchers first used CNO (design drug activated design receptor, dads agonist) to activate qrfp producing neurons. After 30 minutes, the motor activity decreased and lasted for a long time, and the skin temperature (tbat) of the scapular region where the brown adipose tissue (BAT) is located.therefore, qrfp or hypothermia induced neurons are genetic markers.although qrfp producing neurons are specifically distributed in the hypothalamus, they are distributed in several discrete regions.further analysis showed that qrfp was distributed in the anterolateral nucleus (AVPE), medial preoptic area (MPA) and paraventricular nucleus (PVN), but not in LHA.using CNO to activate neurons in AVPE, MPa and PVN will lead to more stable hypothermia and decreased activity.this indicates that AVPE, MPa and neurons in paraventricular nucleus (or "Q neurons") are mainly responsible for inducing hypothermia.the activation of Q neurons resulted in the decrease of tbat hypothermia and body temperature measured in abdomen, along with the significant decrease of oxygen consumption rate, heart rate and blood glucose, and mice showed extremely low amplitude of EEG; however, activation of neurons expressing qrfp mRNA in LHA region had no effect.Q nerve induced hypothermia and hypometabolic state (qiH) lasted for several days; at room temperature of 20 ℃, a single CNO induced qiH (body temperature lower than 30 ℃) lasted for more than 48 hours, and it took about 1 week for oxygen consumption rate to completely return to normal level.the mice recovered from qiH gradually recovered exercise, food intake and body weight, and did not show abnormal behavior. The brain, heart, kidney, liver and muscle were not damaged.the researchers specifically expressed GFP fluorescent protein in Q neurons, and found that GFP positive fibers were observed in several areas of hypothalamus and brainstem, which are related to sympathetic regulation and temperature control, among which the dorsomedial hypothalamus (DMH) receives a large number of q-neuron projections.using photogenetic methods, ssfo was expressed in Q neurons, and light fibers were implanted into AVPE / MPa in Q neurons.laser activated ssfo EYFP + cells rapidly led to obvious hypothermia, lasting for 30 minutes; repeated activation of Q neurons every 30 minutes within 2 hours resulted in more significant hypothermia, and tbat decreased to 22 ℃ at room temperature.putting optical fibers into DMH of q-ssfo mice can effectively reduce tbat, while q-neuron fibers stimulating raphe pallidus (RPA) have a weak effect on tbat.that is to say, Q neurons mainly project to DMH (a small part to RPA) to induce qiH.at the beginning of qiH induction, the tail temperature of mice immediately increased, which indicated that peripheral vasodilation was triggered to release heat during hypothermia.peripheral blood vessels dilate and body temperature does not rise, which indicates that the reference body temperature (TR) or the theoretical set value of body temperature has been reset to a lower than normal value, which is the characteristic of hibernation.through experimental calculation, the researchers found that the thermal conductivity under normal condition and qiH condition was equivalent, which was different from the decrease of thermal conductivity in daytime sleep. Under the condition ofqiH, the heat production decreased significantly, and the reference body temperature decreased significantly.in addition, when the room temperature was 28 ℃, qiH mice showed a more extended posture, which is usually the posture of animals exposed to high temperature; when the room temperature was lower than 12 ℃, the mice returned to sitting position, shivering and significantly increased oxygen consumption.this indicates that although the reference body temperature decreases during qiH, physical function and behavior are still regulated to adapt to changes in ambient temperature.snare mediated neurotransmitter transmission is necessary for the induction of qiH.the researchers analyzed the location of Q neurons and neurotransmitter transporters and divided them into three categories: 1) QE (excitatory) neurons, VGLUT2 (vesicular glutamate transporter 2) positive, 77.9%; 2) Qi (inhibitory) neurons, vggat (vesicular GABA transporter) positive, 7.2%; 3) QH (mixed) neurons, VGLUT2 and VGAT positive, 14.9%.the proportions of the three subgroups were similar in all selected regions, and neurons were mixed with each other. the absence of VGAT in Q neurons did not affect the phenomenon of qiH induced by CNO and the final tbat value, but the initial rate of tbat reduction after CNO injection was significantly slower; when VGLUT2 was absent in Q neurons, CNO could induce the decrease of tbat, but the effect was weaker and the time was shorter. this indicates that glutamatergic and GABAergic neurotransmitters jointly induce qiH. in conclusion, studies have identified neural circuits that can lead mice to hibernation like long-term hypothermia and hypometabolism, and precisely locate their projection areas, temperature regulation mechanisms and exact neurotransmitters, which will help to develop methods for inducing hibernation like state, and have potential application value in non hibernating mammals including humans. At the same time, the following links have been made by: plate makers: 11 references 1. Geiser, F. hibernation. Curr. Biol. 23, r188 – r193 (2013) (2013) 2. Sunagawa, G. A. & amp; Takahashi, M. hypemetabolism during daily workshop in mice is dominated by reduction in reduction in the sensitivity of the regulatory system, SCI. Rep. 6, 37011 (2016) 1. Geiser, F. F. hibernation, curr, 23, r188 – r193 (2013) (2013) 2. Sunagawa, g. a, & amp; Takahashi, M. Himalaya, g. a & amp; Takahashi, M. hydroxytabashi, M. h, M. Himalaya, M. A., sharing, E.D. & D. & D. & D. & D., D. & D., D amp; Swoap, S. J. Central activation of the A1 adenosine receptor in fed mice recapitulates only some of the attributes of daily torpor. J. Comp. Physiol. B 187, 835–845 (2017).