Press Release2021.1.14｜International Institute for Integrative Sleep Medicine (WPI-IIIS)

How the brain paralyzes you while you sleep
Researchers at the University of Tsukuba in Japan have discovered a groupof neurons in the mouse brainstem that suppress unwanted movement
during rapid- eye- movement sleep.
Tsukuba, Japan — We laugh when we see Homer Simpson falling asleep
while driving, while in church, and while even manningoperating thenuclear reactor. In reality though, narcolepsy, cataplexy, and rapid- eyemovement (REM) sleep behavior disorder are all serious sleep-related
illnesses. Researchers at the University of Tsukuba led by Professor Takeshi
Sakurai have found neurons in the brain that link all three disorders andcould provide a target for treatments.
REM sleep icorrelates when we dream. Our eyes move back and forth, but
our bodies remain still. This near-paralysis of muscles while dreaming iscalled REM-atonia, and is lacking in people with REM sleep behavior
disorder. Instead of being still during REM sleep, muscles move around,often going as far as to stand up and jump, yell, or punch. Sakurai and his
team set out to find the neurons in the brain that normally prevent this typeof behavior during REM sleep.
Working with mice, the team identified a specific group of neurons as likely
candidates. These cells were located in an area of the brain called theventral medial medulla and received input from another area called thesublaterodorsal tegmental nucleus, or SLD. “The anatomy of the neurons
we found matched what we know,” explains Sakurai. “They were connected
to neurons that control voluntary movements, but not those that control
muscles in the eyes or internal organs. Importantly, they were inhibitory,
meaning that they can prevent muscle movement when active.” When theresearchers blocked the input to these neurons, the mice began moving
during their sleep, just like someone with REM sleep behavior disorder.

Narcolepsy, as demonstrated by Homer Simpson, is characterized bysuddenly falling asleep at any time during the day, even in mid-sentence (hewas diagnosed with narcolepsy). Cataplexy is a related illness in whichpeople suddenly lose muscle tone and collapse. Although they are awake,
their muscles act as if they are in REM sleep. Sakurai and his team suspectedthat the special neurons they found were related to these two disorders.
They tested their hypothesis using a mouse model of narcolepsy in which
cataplexic attacks could be triggered by chocolate. “We found that silencing
the SLD-to-ventral medial medulla reduced the number of cataplexic bouts,”
says Sakurai.
Overall, the experiments showed these special cellscircuits control muscle
atonia in both REM sleep and cataplexy. “The glycinergic neurons we haveidentified in the ventral medial medulla could be a good target for drug
therapies for people with narcolepsy, cataplexy, or REM sleep behavior
disorder”, says Sakurai. “Future studies will have to examine how emotions,which are known to trigger cataplexy, can affect these neurons.”
About IIIS
IIIS was launched by the Ministry of Education, Culture, Sports, Science andTechnology of Japan with the aim of building globally visible research
centers with high research standards and excellent research environments
to accommodate globally prominent researchers. IIIS is the world’s premierinstitute aiming to elucidate the fundamental principles of sleep/wakebiology, develop new strategies to diagnose, prevent, and treat sleep
disorders, and contribute to promote human health through research
activities. The research was funded by the Japan Society for the Promotionof Science and the Japan Science and Technology Agency.
Bibliographic information
Uchida S, Soya S, Saito YC, Hirano A, Koga K, Tsuda M, Abe M, Sakimura K and Sakurai
T, (2020) A discrete glycinergic neuronal population in the ventromedial medulla thatinduces muscle atonia during REM sleep and cataplexy in mice.
Neuroscience
DOI: http:doi.org/10.1523/JNEUROSCI.0688-20.2020

Media Contact
Alliance and Communication Unit, International Institute for Integrative Sleep Medicine(WPI-IIIS), University of Tsukuba, Japan
E-mail: wpi-iiis-alliance@ml.cc.tsukuba.ac.jp