Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism

Summary: Sleep disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are...

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Main Authors: Ashley Choi, Bowon Kim, Eleanor Labriola, Alyssa Wiest, Yingqi Wang, Jennifer Smith, Hyunsoo Shin, Xi Jin, Isabella An, Jiso Hong, Hanna Antila, Steven Thomas, Janardhan P. Bhattarai, Kevin Beier, Minghong Ma, Franz Weber, Shinjae Chung
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:iScience
Subjects:
Behavioral neuroscience
Molecular neuroscience
Cellular neuroscience
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224025100
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Summary:Summary: Sleep disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine consolidate sleep. Furthermore, inhibiting LC-NE neurons restores memory. Finally, rabies-mediated screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory-regulatory regions in 16p11.2 deletion mice. Our findings identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.
ISSN:2589-0042

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