Muscle Activity During Sleep in Human Subjects, Rats, and Mice: Towards Translational Models of REM Sleep Without Atonia.
Rapid-eye-movement (REM) sleep without atonia (RSWA) is a marker of REM sleep behavior disorder (RBD) and is common in narcolepsy. Available techniques for electromyogram (EMG) analysis are species-specific, limiting translational research on RSWA. We developed an automated technique based on distributions of normalized EMG values (DNE) to overcome this limitation. With DNE, we tested whether the control of neck and tibialis anterior (TA) muscles during sleep in wild-type rats and mice validly models the control of submentalis (chin) and TA muscles in healthy humans. We then applied DNE to REM sleep recordings of patients with idiopathic RBD and of mouse models of narcolepsy, testing for a common DNE signature of RSWA.



Retrospective analysis of sleep recordings from 20 idiopathic RBD patients, 34 control subjects, 8 wild-type rats, 21 orexin-neuron deficient mice, 8 orexin knock-out mice, and 22 wild-type mice.



Neck EMG of rats and mice and human chin EMG progressively decreased from wakefulness to non-REM sleep and REM sleep, whereas the effects of sleep on TA EMG differed between rats, mice, and humans. DNE discriminated idiopathic RBD patients from controls based on higher median values of normalized chin EMG during REM sleep. The same parameter, computed on neck muscle EMG, discriminated narcoleptic mice from wild-type mice.



These results support the application of DNE in translational research on RSWA. Increased median values of normalized EMG of chin (humans) and neck (rats and mice) muscles may be a signature of RSWA in different species and pathological conditions.
PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Alessandro
A
Silvani
Sleep Research Center, Department of Neurology I.C., Oasi Research Institute, Troina, Italy.
Raffaele
R
Ferri
PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Viviana
V
Lo Martire
PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Stefano
S
Bastianini
PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Chiara
C
Berteotti
Laboratory for Biomedical Neurosciences (LBN), Neurocenter of Southern Switzerland, Lugano, Switzerland.
Agnese
A
Salvadè
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.|IRCCS Institute of Neurological Sciences, Bologna, Italy.
Giuseppe
G
Plazzi
Sleep Disorders Center, Department of Neurology, Scientific Institute and University Hospital San Raffaele, Vita-Salute University, Milan, Italy.
Marco
M
Zucconi
Sleep Disorders Center, Department of Neurology, Scientific Institute and University Hospital San Raffaele, Vita-Salute University, Milan, Italy.
Luigi
L
Ferini-Strambi
Center for Experimental Neurology (ZEN) and Department of Neurology, Bern, Switzerland.
Claudio L
CL
Bassetti
Laboratory for Biomedical Neurosciences (LBN), Neurocenter of Southern Switzerland, Lugano, Switzerland.|Sleep and Epilepsy center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano, Lugano, Switzerland.
Mauro
M
Manconi
PRISM Laboratory, Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Giovanna
G
Zoccoli
D000328:Adult; D000818:Animals; D002680:Chin; D004576:Electromyography; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009123:Muscle Hypotonia; D018482:Muscle, Skeletal / Q000502:physiology*; D009333:Neck; D000068797:Orexins / Q000172:deficiency / Q000378:metabolism; D051381:Rats; D012189:Retrospective Studies; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
D000068797:Orexins
Mice; Muscle tonus; Narcolepsy; REM sleep behavior disorder; Rats; Sleep; Translational medical research.