动物造模 z-bo 2020-09-09 556

　　"The sun is basking, it's time for the child to get up!" ——Presumably everyone has had this experience: when you sleep well, suddenly the curtains open and a bright light breaks through the window, and most of you wake up in an instant.

　　It may be difficult for humans to imagine that when nocturnal animals like mice are asleep during the day, if the environment suddenly darkens, they will quickly wake up within a few minutes.

　　What mechanism affects our sleep and wakefulness? The research team of Researcher Huang Zhili and Professor Qu Weimin of Fudan University School of Basic Medicine have been devoted to the investigation of these issues for many years. On January 31, the relevant results were published online in Current Biology. The research team's doctoral students Zhang Ze and Liu Wenying were the first authors of the paper.

　　How did

　　mice wake up "darkly"?

　　Like humans, the photosensitive organ of mice is the retina. The researchers injected a virus that encodes channel light sensitive protein and red fluorescent protein into the eyes of mice. These mice are not ordinary mice. Their γ-aminobutyric acid neurons carry the green fluorescent protein gene, that is, "fluorescent mice."

　　By observing the expression of the fluorescent protein gene carried by the virus, scientists can clearly see the projection of neurons in the area where they have been injected into the body. This method is called "tracing".

　　Through tracing, researchers confirmed that gamma-aminobutyric acid neurons located in the superior colliculus (a structure of the brain) can receive direct functional input from the retina. They exposed the fluorescent mice to different lighting environments and found that such neurons can be inhibited by a short-term dark stimulus, but they will not be affected by light pulses. Furthermore, this neuron can directly inhibit another downstream neuron-dopaminergic neurons in the ventral tegmental area.

　　"It has long been confirmed that dopamine is highly correlated with wakefulness." Huang Zhili, the corresponding author of the paper, explained to a reporter from China Science Daily. "Under dark environment stimulation, the retina is no longer excited and the superior colliculus γ-aminobutyric acid neurons are inhibited. The suppression of the downstream dopaminergic neurons will be lifted, and dopamine will be released. Therefore, the mice will soon wake up in the sudden dark environment."

　　In order to ensure a rigorous conclusion, they also designed a reverse proof experiment-through gene editing, specifically damage the mouse superior colliculus γ-aminobutyric acid neurons or ventral tegmental dopaminergic neurons. At this time, even if the darkness fell suddenly, the mice did not even notice and continued to sleep.

　　Mouse and human, more exploration is needed

　　"In the past, research on the effects of light on sleep was mainly focused on the relationship between light cycle and biological rhythms. The 2017 Nobel Prize in Physiology or Medicine was awarded to scientists who study the mechanism of circadian rhythms." Those who did not participate in this work Duan Shumin, an academician of the Chinese Academy of Sciences and a professor at Zhejiang University, told a reporter from China Science News, "The current feature of this result is that they study how light itself regulates sleep."

　　Interestingly, although human brain and mouse brain have many similarities in structure, humans and mice respond to light in opposite ways in sleep. The more thorough the study of the awakening mechanism of mice is, the more people wonder at which link the diurnal and nocturnal animals are running in opposite directions.

　　"This is indeed a big problem. We currently only have some preliminary understanding and are still exploring further." Huang Zhili said.

　　The Nile grass rat is a diurnal rodent and is the best model to study this problem. They hope that in the future, through research on Nile grass mice, they can answer why diurnal and nocturnal animals respond to light in opposite directions.

　　Use light as the key to save sleep well

　　Staying up late to chase dramas, partying all night, working overtime, traveling across time zones...As people’s entertainment life becomes more and more trendy and work pressure is increasing, the incidence of sleep disorders caused by biological rhythm disorders is increasing year by year. And "light" plays a vital role in it.

　　For many years, Huang Zhili and his team have been pursuing the relationship between light and sleep.

　　Why do manual workers sleep better than mental workers? Because physical labor consumes a lot of energy, the metabolite of energy ATP is adenosine, which acts on adenosine receptors, making people indulge in dreams.

　　Go to the bathroom in the middle of the night, and can't receive it when you come back? It is best to replace the night light at home with a low-power red light to see the route clearly and save sleepiness.

　　Why do Parkinson's patients often have severe sleep disorders? Because they have severe basal ganglia disease.

　　Why drinking coffee keeps you awake? Because coffee can block adenosine receptors.

　　……

　　At a time when the old, middle-aged and young people are crying "not sleeping well," these research results are obviously of great practical significance.

　　So what is the reference for humans from the results of mice being "darkly awakened"?

　　Huang Zhili said: "The abnormal light that is common in modern life can disrupt biological rhythms and cause sleep disorders. Although the sleep and wakefulness conditions of nocturnal animals are opposite to those of humans, it is sufficient to prove that the above-mentioned neural structure plays an important role in this process. We hope that these studies can provide ideas for clinical exploration and treatment of sleep disorders with biological rhythm disorders, such as the development of specific targeted drugs, or physical therapies such as magnetic therapy, ultrasound, microwave, etc., to act on these targets to prevent poor sleep. People light up new hope."