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Volume transmission is the major mode for 5-HT transmission but mechanisms underlying 5-HT signaling are still largely unknown. Abnormal brain 5-HT levels and function have been implicated in autism spectrum disorder (ASD). Neurexin (\n                    <jats:italic>Nrxn<\/jats:italic>\n                    ) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in\n                    <jats:italic>Nrxn<\/jats:italic>\n                    genes are associated with neurodevelopmental disorders including ASD. However, the role of\n                    <jats:italic>Nrxn<\/jats:italic>\n                    genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three\n                    <jats:italic>Nrxn<\/jats:italic>\n                    genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of\n                    <jats:italic>Nrxns<\/jats:italic>\n                    in 5-HT neurons reduced the number of serotonin neurons in the early postnatal stage, impaired 5-HT release, and decreased 5-HT release sites and serotonin transporter expression. Furthermore, 5-HT neuron-specific\n                    <jats:italic>Nrxn<\/jats:italic>\n                    knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission, 5-HT neuron survival, and the execution of complex behaviors.\n                  <\/jats:p>","DOI":"10.7554\/elife.85058","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:00:10Z","timestamp":1674619210000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85058","source":"Crossref","is-referenced-by-count":23,"title":["Neurexins in serotonergic neurons regulate neuronal survival, serotonin transmission, and complex mouse behaviors"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4708-0293","authenticated-orcid":true,"given":"Amy","family":"Cheung","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurobiology, University of Massachusetts Chan Medical School","place":["Worcester, United 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