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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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224025100 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Ashley Choi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-21051ff035244a1b8b7c45be4724d653 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-21051ff035244a1b8b7c45be4724d6532025-08-20T02:35:05ZengElsevieriScience2589-00422024-12-01271211128510.1016/j.isci.2024.111285Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autismAshley Choi0Bowon Kim1Eleanor Labriola2Alyssa Wiest3Yingqi Wang4Jennifer Smith5Hyunsoo Shin6Xi Jin7Isabella An8Jiso Hong9Hanna Antila10Steven Thomas11Janardhan P. Bhattarai12Kevin Beier13Minghong Ma14Franz Weber15Shinjae Chung16Department of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA 92617, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Neuroscience, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224025100Behavioral neuroscienceMolecular neuroscienceCellular neuroscience |
| spellingShingle | 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 Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism iScience Behavioral neuroscience Molecular neuroscience Cellular neuroscience |
| title | Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism |
| title_full | Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism |
| title_fullStr | Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism |
| title_full_unstemmed | Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism |
| title_short | Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism |
| title_sort | circuit mechanism underlying fragmented sleep and memory deficits in 16p11 2 deletion mouse model of autism |
| topic | Behavioral neuroscience Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224025100 |
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