TY - JOUR
T1 - A discrete glycinergic neuronal population in the ventromedial medulla that induces muscle atonia during REM sleep and cataplexy in mice
AU - Uchida, Shuntaro
AU - Soya, Shingo
AU - Saito, Yuki C.
AU - Hirano, Arisa
AU - Koga, Keisuke
AU - Tsuda, Makoto
AU - Abe, Manabu
AU - Sakimura, Kenji
AU - Sakurai, Takeshi
N1 - Funding Information:
This work was supported by the JSPS KAKENHI Grant-in-Aid for JSPS Fellows 18J21114 (to S.U.), JSPS KAKENHI Grants-in-Aid for Scientific Research (B) JP 15H03122 and 18H02595 (to T.S.), the KAKENHI Grant-in-Aid for Exploratory Research JP 15K12768 (to T.S.), and the KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas “Willdynamics” 16H06401 (to T.S.). We thank Dr. Kazunari Miyamichi and Mr. Masatoshi Kasuya for technical advice. The authors declare no competing financial interests. Correspondence should be addressed to Takeshi Sakurai at sakurai.takeshi.gf@u.tsukuba.ac.jp. https://doi.org/10.1523/JNEUROSCI.0688-20.2020 Copyright © 2021 the authors
Publisher Copyright:
© 2021 Society for Neuroscience. All rights reserved.
PY - 2021/1/17
Y1 - 2021/1/17
N2 - During rapid eye movement (REM) sleep, anti-gravity muscle tone and bodily movements are mostly absent, because somatic motoneurons are inhibited by descending inhibitory pathways. Recent studies showed that glycine/GABA neurons in the ventromedial medulla (VMM; GlyVMMneurons) play an important role in generating muscle atonia during REM sleep (REM-atonia). However, how these REM-atonia-inducing neurons interconnect with other neuronal populations has been unknown. In the present study, we first identified a specific subpopulation of GlyVMMneurons that play an important role in induction of REM-atonia by virus vector-mediated tracing in male mice in which glycinergic neurons expressed Cre recombinase. We found these neurons receive direct synaptic input from neurons in several brain stem regions, including glutamatergic neurons in the sublaterodorsal tegmental nucleus (SLD; GluSLDneurons). Silencing this circuit by specifically expressing tetanus toxin light chain (TeTNLC) resulted in REM sleep without atonia. This manipulation also caused a marked decrease in time spent in cataplexy-like episodes (CLEs) when applied to narcoleptic orexin-ataxin-3 mice. We also showed that GlyVMMneurons play an important role in maintenance of sleep. This present study identified a population of glycinergic neurons in the VMM that are commonly involved in REM-atonia and cataplexy.
AB - During rapid eye movement (REM) sleep, anti-gravity muscle tone and bodily movements are mostly absent, because somatic motoneurons are inhibited by descending inhibitory pathways. Recent studies showed that glycine/GABA neurons in the ventromedial medulla (VMM; GlyVMMneurons) play an important role in generating muscle atonia during REM sleep (REM-atonia). However, how these REM-atonia-inducing neurons interconnect with other neuronal populations has been unknown. In the present study, we first identified a specific subpopulation of GlyVMMneurons that play an important role in induction of REM-atonia by virus vector-mediated tracing in male mice in which glycinergic neurons expressed Cre recombinase. We found these neurons receive direct synaptic input from neurons in several brain stem regions, including glutamatergic neurons in the sublaterodorsal tegmental nucleus (SLD; GluSLDneurons). Silencing this circuit by specifically expressing tetanus toxin light chain (TeTNLC) resulted in REM sleep without atonia. This manipulation also caused a marked decrease in time spent in cataplexy-like episodes (CLEs) when applied to narcoleptic orexin-ataxin-3 mice. We also showed that GlyVMMneurons play an important role in maintenance of sleep. This present study identified a population of glycinergic neurons in the VMM that are commonly involved in REM-atonia and cataplexy.
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U2 - 10.1523/JNEUROSCI.0688-20.2020
DO - 10.1523/JNEUROSCI.0688-20.2020
M3 - Article
C2 - 33372061
AN - SCOPUS:85102212585
VL - 41
SP - 1582
EP - 1596
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 7
ER -