Science: Solve decades of challenges! Xu Min first discovered the important role of glutamate energy neurons in sleep stabilization regulation.

Sleep stability is the balance between sleep duration and wakefulness and is a basic feature of the sleep-wake cycle.
during waking, sleep-promoting factors build up and lead to increased sleep stress or we need sleep.
decades of research have identified many genes, molecules, and bio-chemical processes associated with sleep stability.
in various processes related to sleep stability, adenosine is an important part of cell metabolic pathways and an important physiological medium for sleep stability.
adenosine released in the substrate foremost brain (BF) plays a vital role in regulating the sleep-wake cycle, inhibiting nerve activity mediated by A1 subjects and increasing sleep stress.
addition, the sleep-wake cycle is controlled by different patterns of neural activity in the brain, but it is not clear how this neural activity promotes balance in the sleep body.
, September 4, 2020, the Xu Min team of the Institute of Neurology of the Chinese Academy of Sciences published a research paper on Science Online entitled "Regulation of Sleep homeostasis mediator adenosine by basal forebrain glutamatergic neurons", Using the new genetically coded adenosine probe, the study found that glutamate-energy neurons in the pre-brain region of the substrate play an important role in regulating the accumulation of sleep stress, and further reveal the neural loop mechanism of sleep steady-state regulation, which provides an important reference for exploring the treatment of sleep disorders.
is a common phenomenon in the animal world, and humans spend about a third of their time sleeping.
it is not clear how sleep is regulated.
classical sleep regulation model, sleep regulation is divided into two aspects, circadian rhythm and sleep stability.
the circadian rhythm controls the time of the day's sleep awakening through the inner biological clock, and sleep stability is mainly regulated by sleep stress, which controls the amount of sleep the body gets.
sleep stress increases as waking hours progress, and as sleep progresses, sleep stress is gradually removed.
the sleep-stabilizing system works when sleep is disturbed, for example, by staying up late and sleeping more "scented" and for longer periods of time.
At present, the mainstream theory holds that adenosine is involved in the process of sleep stabilization regulation, and its accumulation in a sober state leads to the production of "difficulty", while caffeine, the main ingredient of coffee, can promote sobriety by blocking the binding of adenosine to its receptors.
substrate prec brain is considered to be an important brain region in which adenosine is involved in sleep stabilization regulation, and studies at the loop level show that local neural loops in this region are involved in the regulation of sleep awakening, but the mechanism by which neuron activity regulates adenosine release is not yet known.
this limits the in-depth analysis of the mechanism of sleep awakening regulation.
In order to detect the high spatial-time resolution of extracellular adenosine concentrations in the precland brain region of the substrate during the sleep awakening cycle, Li's team developed a new genetically coded adenosine probe that converts changes in extracellular adenosine concentrations into rapid changes in probe fluorescence intensity.
Using the adenosine probe, Xu Min's team found that adenosine concentrations in the pre-brain region of the substrate were higher when awake and lower during non-rapid eye movement sleep, consistent with previous studies that measured changes in adenosine concentration using microdialysis.
, however, the mice had shorter periods of rapid eye movement sleep, and traditional microdialysis methods could not accurately measure adenosine concentration during rapid eye movement sleep.
thanks to the probe's high time resolution, Xu Min's team found for the first time that adenosine also had high concentrations during fast eye movement sleep and was higher than awake and non-rapid eye movement sleep.
, the researchers observed rapid changes in adenosine concentrations during sleep phase transitions, suggesting that they were closely related to neuron activity.
To further explore the relationship between increased adenosine concentration and neuron activity, Xu Min's team explored two types of neurons in the pre-brain region of the substrate: acetylcholine-energy neurons and glutamate-energy neurons and adenosine concentration changes in correlation and causality.
results showed that calcium activity of these two neurons was highly associated with extracellular adenosine concentrations, and that nerve activity was always released ahead of adenosine.
these two neurons can cause different degrees of increase in extra-cytosine concentration, and glutamate energy neuron activation is the main reason for the increase in adenosine concentration.
further, the researchers specificated the destruction of glutamate-energy neurons in the frontal brain region of the substrate, and the results showed that the increase in extracellular adenosine concentration was significantly lower than in the control group mice.
above tests show that the activities of glutamate-energy neurons are involved in regulating the accumulation of extracellular adenosine.
Previous studies have shown that impaired adenosine accumulation in the pre-brain region of the substrate can lead to abnormal adjustment of sleep steady state, and based on the above experimental results, Xu Min's team speculated that the absence of glutamate-energy neurons in the pre-brain region of the substrate may affect sleep stability.
results showed that the sleep stress of mice with glutamate-energy neurons missing in the pre-brain region of the substrate decreased significantly (a significant increase in waking time) and that sleep stability also changed - the increase in sleep length after sleep deprivation was significantly lower than in the control group mice, and the rate of sleep stress was significantly faster than in the control group mice.
above experiments show that glutamate-energy neurons in the frontal brain region of the substrate play an important role in regulating the accumulation of sleep stress.
this study reveals the important role played by glutamate-energy neurons in the pre-brain region of the substrate in the accumulation of sleep stress in the mediated sobriety state, and lays a solid foundation for further study of the mechanism of sleep steady-state regulation.
The study was conducted by PhD candidates Peng Wanling and Songunder the guidance of Xu Min, a researcher at the Center of Brain And Intelligence Excellence of the Chinese Academy of Sciences, and was carried out by researcher Li Weilong of Peking University, Dr. Wu Zhaohua and Zhang Siyu of Shanghai Jiaoxuan University School of Medicine.
project has been supported by the Chinese Academy of Sciences, the Ministry of Science and Technology, the Fund Committee, the Shanghai Science and Technology Commission, the Beijing Municipal Science and Technology Commission and the Guangdong Provincial Science and Technology Commission.
.