title: Neurexin regulates nighttime sleep by modulating synaptic transmission.
abstract: Neurexins are cell adhesion molecules involved in synaptic formation and synaptic transmission. Mutations in neurexin genes are linked to autism spectrum disorders (ASDs), which are frequently associated with sleep problems. However, the role of neurexin-mediated synaptic transmission in sleep regulation is unclear. Here, we show that lack of the Drosophila α-neurexin homolog significantly reduces the quantity and quality of nighttime sleep and impairs sleep homeostasis. We report that neurexin expression in Drosophila mushroom body (MB) αβ neurons is essential for nighttime sleep. We demonstrate that reduced nighttime sleep in neurexin mutants is due to impaired αβ neuronal output, and show that neurexin functionally couples calcium channels (Cac) to regulate synaptic transmission. Finally, we determine that αβ surface (αβs) neurons release both acetylcholine and short neuropeptide F (sNPF), whereas αβ core (αβc) neurons release sNPF to promote nighttime sleep. Our findings reveal that neurexin regulates nighttime sleep by mediating the synaptic transmission of αβ neurons. This study elucidates the role of synaptic transmission in sleep regulation, and might offer insights into the mechanism of sleep disturbances in patients with autism disorders.
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing 210096, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Tong
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing 210096, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing 210096, China.
authors.forename: Zi Chao
authors.initials: ZC
authors.lastname: Zhang
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing 210096, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Life Sciences, Key Laboratory of Developmental Genes and Human Diseases, Southeast University, Nanjing 210096, China.|Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China.
authors.forename: Junhai
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D004325:Dreams / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D006801:Humans; D024521:Mushroom Bodies / Q000378:metabolism*; D009154:Mutation; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C491321:Nrx protein, Drosophila