The more stress, the more sleepy I get

Sleep, what countless migrant workers and school dogs lack. But its presence is so strong that every time we ignore it, the brain and body will issue a warning with a terrible headache.

Studies show sleep strengthens memories, clears waste products from the brain and body, boosts immunity, and more, so you’re ready for a new day. Lack of sleep for a long time will affect people’s memory, mood, physical metabolism, etc. In severe cases, they may even suffer from diabetes, cardiovascular disease, cancer and neurological diseases early.

Actually,During the process of lying down – closing your eyes – falling asleep, we will unconsciously inhibit body movement, slow down heart rate, dilate blood vessels, and thus lower blood pressure. It can be said that nothing is more soothing than sleep. However, for a long time, we did not know why sleep is closely related to changes in heart rate and blood pressure.

Thesis title:

Cardiovascular baroreflex circuit moonlights in sleep control



Recently, the team of Professor Yang Dan from the University of California, Berkeley found that the main neurons in the baroreflex circuit (Baroreflex) that regulates the cardiovascular system are also involved in sleep regulation. Simply put, arterial blood pressure increases, and information is transmitted to the nucleus pulposus solitarius through peripheral baroreceptors (NST), NST neuron activation not only regulates vasomotion and reduces heart rate , can also effectively promote non-rapid eye movement sleep in mice (NREM).

The research team first wanted to find and label the neurons in the NST that are involved in the cardiovascular baroreflex circuit. In this experiment, they used a TRAP system (Fos-iCreER x LSL-tdTomato) previously designed by Luo Liqun’s lab to capture neurons participating in the circuit.

First, they used the vasoconstrictor-phenylephrine (PE) to activate the baroreflex circuit, and then the activated neurons in the circuit were in 4 hydroxytamoxifen (4-hydroxytamoxifen, 4- Under the blessing of OHT), Cre will be expressed due to the expression of Fos, and the expression of Cre can cause the expression of fluorescent protein. In short, the fluorescent protein-labeled NSTPE-TRAP neurons are the small group involved in the blood pressure sensory reflex loop.

By further fluorescence in situ hybridization, they found that a large fraction of the labeled NST neurons expressed cocaine and amphetamine-regulated transcription peptide (CART). So they also labeled and detected NSTCART neurons at the same time. Similar to NSTPE-TRAP neurons, their activity closely matches the fluctuation rhythm of heartbeat and blood pressure. Then, through the reverse tracing technique, the researchers further confirmed that these neurons can directly receive excitation signals from the upstream baroreceptors Piezo1 and Piezo2.

Designed and provided by Yuanyuan Yao, the first author of this paper.

In order to further explore whether these NSTPE-TRAP neurons are involved in the sleep regulation of NREM, the researchers activated NSTPE-TRAP and NSTCART neurons through chemical genetic regulation and optogenetic regulation, and found that small The rats’ blood pressure and heartbeat were reduced, and NREM sleep was significantly improved. Conversely, inhibiting these neurons promotes arousal and reduces NREM.

The researchers then more fully explored the downstream projection neurons of NSTPE-TRAP and NSTCART neurons, including inhibitory neurons in the caudal ventrolateral medulla (CVLM) and more The lower excitatory adrenergic sympathetic neurons of the rostral ventrolateral medulla (RVLM) are inhibited by the CVLM, and of course the cholinergic parasympathetic neurons of the intramedullary nucleus doubtful (Amb). Whether optogenetically activate inhibitory neurons of CVLM, or inhibit neurons of RVLM, orIt is chemical activation of Amb neurons, which will play a similar role in promoting NREM sleep.

Overall, this study reveals that the circuits commonly thought to regulate cardiovascular stress are actually doing a secondary role in promoting sleep. According to the first author, Dr. Yuanyuan Yao, although previous studies have shown that stimulating baroreceptors in anesthetized animals does induce a sleep-like state. But over the years, there has not been more work to explain this phenomenon in more detail, so that most people may have forgotten the relevant results. And this recent discovery not only found a similar phenomenon in freely moving mice, but also deepened our understanding of baroreflex and sleep at the circuit level, providing new ideas for future non-invasive sleep enhancement technologies.

Still struggling to report for tomorrow’s project? Are you still being “supported” by the exploding melon that was brushed ten minutes ago? Come and try the newly released pressure receptors, as long as you dare to “press”, you can sleep well.

Author: Tutu | Cover: Yuanyuan Yao

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