Nature back-to-back: is it subversion or integration? A new breakthrough has been made in the field of thermothemes regulation nerves.

Learn about the latest advances in neuroscience ● click on the blue letter to focus on us ● mammalian body temperature is precisely regulated by the brain, and is generally maintained at an average core temperature (usually about 37 ° C) throughout life, with fluctuations within 0.5 ° C.however, lack of food can cause some mammals to enter a state similar to sleep, and their body temperature may drop by 5 – 10 ° C. according to the duration of sleep, they can be divided into hibernation and diurnal hibernation (1).the preoptic anterior hypothalamus is the key center of thermoregulation. There are heat sensitive neurons and cold sensitive neurons that respond to hot stimulation.in winter, the fish are not so active, and the snake also hides in the cave to hibernate.these animals reduce their energy consumption by lowering their body temperature, thus alleviating the food shortage in winter.of course, some animals sleep in summer, which is called Summer sleep.among them, the longest hibernating animal in a year is the Dormouse, which can last up to 9 months, which is really worthy of the name.in fact, Japanese scientists found a hibernation specific protein (HP) in the blood of hibernating Chipmunks. This protein changes with the time of hibernation and changes periodically.specifically, the level of HP protein in the blood was low before the animals fell asleep and remained low throughout the hibernation period.when they wake up, the level goes up again.but in cerebrospinal fluid, the opposite is true: HP levels rise after sleep, revealing the molecular mechanism of hibernation regulation (2).let's take a look at the neural loop mechanisms that regulate hibernation today! On June 11, 2020, a back-to-back article published in nature revealed the neural loop that regulates the hibernation like behavior of experimental mice and completely changed the cognition of the preoptic area anterior hypothalamus, which is the core of temperature regulation.first, let's look at the first article published in nature by Takeshi Sakurai research team from the medical department of Tsukuba University and the international comprehensive sleep medicine research institute, revealing that activating hypothalamic neuropeptide qrfp induces hibernation like behavior in mice (3).the neuropeptide qrfp (a member of RFA peptide family, which is the endogenous ligand of orphan receptor grp103) is enriched and expressed in the hypothalamus and participates in the regulation of body temperature.chronic activation of qrfp expressing neurons (hereinafter referred to as Q neurons) in the hypothalamus by researchers through chemical genetics technology led to the loss of activity of animals, and the body temperature dropped to about 23 – 24 ° C for up to 48 hours, showing a similar hibernation like behavior. After recovering from this state, mice did not have obvious tissue and organ damage or behavioral abnormalities.it was further found that this hypothermia is associated with decreased heart rate and respiratory rate as well as decreased metabolic rate.these studies suggest that activation of Q neurons induces hibernation like behavior. previous studies have shown that it promotes hyperthermia and the dorsomedial hypothalamus (DMH) receives abundant q-neuron projections. researchers activated the soma or axon terminals of Q neurons in the DMH brain region through photogenetic technology, which could cause hibernation like behavior for about half an hour. the body temperature of the mice dropped to 22 ° C after being activated by light every 30 minutes within 2 hours. interestingly, the body temperature of animals with q-neuron induced hypothermia is still in the state of regulation, but the range of regulation is small. this further indicates that other non-Q preoptic neurons can continue to regulate body temperature when Q neurons actively reduce body temperature, but the level is limited. the neurotransmitter characteristics of Q neurons, the picture is from literature 3, so Q neurons are excitatory or inhibitory neurons? The answer is both. immunofluorescence showed that 77.9% of the neurons were excitatory neurons, accounting for the majority; 7.2% of the neurons were inhibitory neurons, but most of them were not useful. further knockout of the excitatory neurotransmitter VGLUT2 or the inhibitory neurotransmitter vggat can cause the low metabolism state of mice, but the low metabolism effect caused by the knockout of the inhibitory neurotransmitter VGAT is stronger. in general, this study reveals that there is a special type of neurons in the hypothalamus, Q neurons, which regulate hibernation like behavior. in fact, the experimental mice often used in scientific research do not hibernate, but these mice have diurnal hibernation, showing short-term hypometabolism. in another paper, Michael E. Greenberg's team from the Department of neuroscience, Harvard University School of medicine, found a new class of neurons that regulate the diurnal sleep of mice: ADCYAP1 neurons (4) in the avmlpa brain region. through a 24-hour food deprivation experiment, the researchers induced diurnal sleep in mice, which was characterized by a significant decrease in metabolic rate and activity, and a body temperature in the range of 24 – 35
C. through brain mapping combined with artificial intelligence technology, it was found that neurons in multiple subregions of hypothalamus were activated during the process of sleep induced by food deprivation. using fluorescent labeling technology, researchers can label these activated neurons. In addition, reactivation of these neurons by chemical genetic techniques can cause sleep in mice even if food deprivation is no longer given. one of the key and magical brain regions, avmlpa (full name: antioxidant and ventral regions of the media and lateral reoptic area, which is difficult for me only with high school education), the temperature drop of this brain area can reach 4.9
C, with the largest drop, which has great research potential. therefore, the researchers further found that the largest number of neurons related to sleep was ADCYAP1 expressing neurons. chronic and specific activation of ADCYAP1 neurons in avmlpa brain region through chemical genetics can cause a significant drop in body temperature in mice, but it can not be caused by chronic inhibition of this type of neurons even in the case of food deprivation. this study revealed the key role of ADCYAP1 neurons in the regulation of body temperature in avmlpa brain region, which laid a foundation for exploring the neural loop mechanism of regulating extreme hypothermia and extreme metabolism in the future. so how did these two articles change the cognition of thermoregulation? The classical and non classical pathways of heat production, pictures from references 1. In the past, classic neural circuits suggested that the increase of body surface temperature activated the excitatory neurons in the central preoptic nucleus (mnpo), and further activated the inhibitory neurons in the adjacent medial preoptic area (MPOA) of the hypothalamus to generate and store heat. The inhibitory projections of MPOA brain area projected to the nucleus raphe pallidus and hypothalamus Dorsomedial brain (DMH). these two articles found that non classical ways to regulate body temperature: ADCYAP1 (adenylate cyclase activating peptide) positive glutamatergic neurons in MPOA brain region and qrfp neurons in MPOA brain area can directly regulate body temperature. References: 1. Flipping the switch on the body's thermal system, a discrete neural circuit leads a hibernation like state in roots, nerves that regulate mouse torpor,