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<i title="Cold Spring Harbor Laboratory">
<span class="release-stage" >pre-print</span>
Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in both humans and mice. Here, we further explore the processes of sleep regulation<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1101/809822">doi:10.1101/809822</a> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/oyhc55t77ffxlnaypwnhtddbfi">fatcat:oyhc55t77ffxlnaypwnhtddbfi</a> </span>
more »... studying the PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused on microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles within NREM sleep. While the former are thought to contribute to neuronal network formation early in brain development, the latter are markers of thalamocortical processes. Both signals are often compromised in neurodevelopmental disorders and influence functional properties of cortical neurons. Thus, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array (MEA) studies. Our results indicate that the Snord116 gene in mice selectively influences REM sleep properties, such as theta rhythms and the organization of REM episodes throughout sleep-wake cycles. Moreover, sleep spindles present specific abnormalities in PWS model systems, indicating that these features of sleep may translate as potential biomarkers in human PWS. We observed abnormalities in the synchronization of cortical neuronal activity that are accounted for by high levels of norepinephrine. In conclusion, our results provide support for an important role of Snord116 in regulating brain activity during sleep and, in particular, cortical neuronal properties, thereby opening new avenues for developing interventions in PWS.
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