Narcolepsy, Cataplexy, and rapid eye movement (REM) sleep behavior disorder are sleep-related severe illnesses.
Scientists at the University of Tsukuba led by Professor Takeshi Sakurai have discovered neurons in the brain that link all three disorders. The discovery offers a target for possible treatments.
During REM Sleep, our eyes move back and forth, but our bodies remain still. This near-paralysis of muscles while dreaming is called REM-atonia and lacks 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.
Scientists conducted their study on mice brains. They identified a specific group of neurons as likely candidates. These cells were situated in an area of the brain called the ventral medial medulla and got a contribution from another region called the sublaterodorsal tegmental core, or SLD.
Sakurai said, “The anatomy of the neurons we found matched what we know. 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 scientists blocked these neurons’ input, the mice began moving during their sleep, just like someone with REM sleep behavior disorder.
Narcolepsy is a sleep disorder characterized by excessive sleepiness. A person with Narcolepsy suddenly falls asleep at any time during the day, even in mid-sentence. On the other hand, Cataplexy is a sudden, brief loss of voluntary muscle tone triggered by strong emotions such as laughter. Although they are awake, their muscles act as if they are in REM sleep.
Scientists suspected that 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.
Sakurai said, “We found that silencing the SLD-to-ventral medial medulla reduced the number of cataplexic bouts.”
“Overall, the experiments showed these special circuits control muscle atonia in both REM sleep and Cataplexy. The glycinergic neurons we have identified in the ventral medial medulla could be a good target for drug therapies for people with narcolepsy, Cataplexy, or REM sleep behavior disorder. Future studies will have to examine how emotions, which are known to trigger Cataplexy, can affect these neurons.”
- Shuntaro Uchida et al. A discrete glycinergic neuronal population in the ventromedial medulla induces muscle atonia during REM sleep and cataplexy in mice. DOI: 10.1523/JNEUROSCI.0688-20.2020