Natural short sleep refers to the sleep habit that the average sleep time is less than 6.5 hours without external pressure and drugs, and there is no detectable and conscious adverse physiological reaction. Why can these people sleep less and not be sleepy? What gives them this enviable ability to envy and hate?
June 5438+1October 65438+may, 2020, Fu and Louis J. Pata of the University of California, San Francisco, USA? As a correspondent of * * *(Cell magazine), Ek published a research paper entitled: Mutation of metabotropic glutamate receptor 1 contributes to natural short sleep characteristics.
In this study, two different mutations were found in the same gene-metabotropic glutamate receptor 1 (GRM 1) that causes natural short sleep. More importantly, both humans and mice carrying this gene mutation show short sleep behavior. Brain slices show that both mutations change the neural characteristics of the brain, increase excitatory synaptic transmission, and lead to short sleep phenotype.
As we all know, for most adults, 7-8 hours' sleep a day is necessary to keep their physical and mental health, but for natural short sleepers (NSSs), 4-6 hours' sleep a day is enough and will not have any obvious negative impact on their health.
It is an indisputable fact that the regulation mechanism of sleep is a very complicated process. Therefore, in order to understand the mechanism leading to this difference between natural short sleepers and normal sleepers, Fu and Louis Ta? The research team led by ek *** has been looking for genetic variations that lead to short sleep behavior.
In this study, the researchers reported that mutations at two different sites of GRM 1 gene were found in two unrelated natural short sleep (FNSS) families. These mutations encode metabotropic glutamate receptor -MGLURS, which usually exists in the cell membrane in the form of dimer.
Previous studies have shown that mGluR 1/5 is involved in a wide range of physiological processes and is related to sleep regulation. More importantly, mGluR5 knockout mice showed serious sleep-wake homeostasis disorder. However, despite these related studies, there is no direct evidence that mGluR 1 plays a role in sleep regulation.
It is worth noting that glutamate is an excitatory neurotransmitter, but in most cases, the activation of metabotropic glutamate receptors will down-regulate the activity of ionic glutamate receptors. Therefore, if GRM 1 mutation leads to receptor dysfunction, glutamate-mediated excitatory synaptic transmission should be up-regulated in neurons expressing the gene.
In this regard, the research team first confirmed through a series of experiments in vitro that both mutations show the loss of receptor-mediated signal transduction function, which indicates that GRM 1 mutation can indeed affect the excitatory synaptic transmission of related neurons.
Then, the research team established GRM 1 mutant mice model through CRISPR gene editing technology, and recorded and analyzed the sleep state of these mice. They found that the GRM 1 mutation can lead to changes in sleep duration-GRM1mutant mice sleep for about half an hour shorter than normal mice.
In addition, in the related electrophysiological experiments, the researchers observed the up-regulation of excitatory synaptic transmission mediated by glutamate in brain slices of GRM 1 mutant mouse model, which once again confirmed that GRM 1 mutation led to the decline of receptor function. In other words, these two mutations change the neural characteristics of the brain and increase the transmission of excitatory synapses.
In fact, Professor Fu and others have made similar findings before-both 1 and NPSR 1 mutants can increase the excitability of cells, suggesting the possibility that short sleep gene mutation can prolong the waking time by up-regulating the excitability of neurons.
Unfortunately, the research team compared the previously discovered short sleep genes-ADRB 1 and NPSR 1, and the sleep time of mouse models of these two genes was shortened by about1hour. Therefore, compared with them, the short sleep phenotype caused by GRM 1 mutation is slightly weak.
Based on this, the author suggests that other genetic factors may cooperate with GRM 1 mutation to change the required sleep duration. In the future, they will reveal this possibility by constructing a variety of mutant mouse models.
In a word, this study shows that GRM 1 is another short sleep gene, and people and mice with this gene mutation will show shorter sleep duration. At the same time, the study also emphasized the important role of metabotropic glutamate receptor -MGLURS in regulating human sleep.
Paper link:
https://doi . org/ 10. 10 16/j . cub . 2020 . 09 . 07 1