Suspension of REM sleep neonucleus and loop mechanism

Sleep consists of
two phases: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep.
REM sleep is closely related to memory consolidation, emotional disorders, neurodegenerative diseases, stress stress, etc.
, but the neurobiological mechanism of REM sleep occurrence and termination is unknown
.
Clinically, patients with narcolepsy characterized by neuronal degeneration of hypothalamic orexin often have cataplexy in the awake state, accompanied by REM-like sleep phenotypes
such as elevated theta waves of EEG signals and loss of muscle tone.
The mechanism of cataplexy and intervention strategies need to be elucidated
.

On October 25, 2022, Professor Huang Zhili's team from the Department of Pharmacology published a paper in the journal Cell Discovery, reporting the mechanism of terminating the new nucleus of REM sleep and neural circuits, and found that GABAergic neurons located in the dorsal part of the midbrain nucleus (dDpMe) in the deep brain stem can efficiently terminate REM sleep, prevent REM sleep from being too long, and reduce the occurrence
of narcolepsy cataplexy.

Researchers Chen Zeka, Dong Hui and Liu Chengwei found that specific activation of dDpMe GABAergic neurons can quickly terminate REM sleep and promote the conversion of REM to NREM sleep through fiber calcium signal recording, in vivo and ex vivo electrophysiological recording, optogenetics, chemogenetics and RNA interference.
On the contrary, inhibition of such neurons can induce the occurrence
of REM sleep.
Using multi-channel in vivo recording technology and according to the electrophysiological release characteristics of neurons, GABAergic neurons in dDpMe were divided into two types of cell populations, type 1 and type 2, and it was clarified that type 1 neurons had the lowest
firing activity during REM sleep.
In order to elucidate the neural pathways of dDpMe GABAergic neurons, the researchers used neural tracing and optogenetic regulation methods to discover that GABA-ergic neurons in dDpMe regulate REM sleep
by projecting to nerve fibers in the lower part of the dorsal tegmental nucleus (SLD) and lateral hypothalamus (LH).
Its downstream glutamatergic neurons in SLD nuclei play a key role in REM regulation, elucidating the new neural circuit mechanism
of REM sleep regulation.

By specifically damaging the hypothalamic orexin neurons in mice, the researchers successfully constructed a mouse cataplexy model, which induced cataplexy when the mice were fed chocolate.
The specific activation of dDpMe GABAergic neurons by optogenetic technology can effectively prevent cataplexy attacks, and mice maintain normal muscle tone
.
This discovery is of great significance for interpreting the pathophysiological mechanism of cataplexy, and establishing a method for selective regulation of dDpMe GABAergic neuronal activity, which has potential translational value
for clinical intervention of cataplexy.

Article information and links:

Ze-Ka Chen#, Hui Dong#, Cheng-Wei Liu#, Wen-Ying Liu, Ya-Nan Zhao, Wei Xu, Xiao Sun, Yan-Yu Xiong, Yuan-Yuan Liu, Xiang-Shan Yuan, Bing Wang, Michael Lazarus, Yoan Chérasse, Ya-Dong Li, Fang Han, Wei-Min Qu*, Feng-Fei Ding* and Zhi-Li Huang*.
A cluster of mesopontine GABAergic neurons suppresses REM sleep and curbs cataplexy.
Cell Discovery.
2022 Oct 25; 8(1):115.
doi: 10.
1038/s41421-022-00456-5.
.

Article author and fund support:

Professor Huang Zhili, Ding Fengfei Young Researcher and Professor Qu Weimin of the Department of Pharmacology are the co-corresponding authors of this paper, and Chen Zeka, Dong Hui and Liu Chengwei of the research group are the co-first authors
of the paper.
The research was supported
by the major project of "Brain Science and Brain-like Research", the National Natural Science Foundation of China and the Frontier Innovation Center of Brain Science.

(Provided by Sleep Research Group)