Department of Neurobiology; Brudnick Neuropsychiatric Research Institute; Futai Lab; Graduate School of Biomedical Sciences
Behavioral Neurobiology | Cognitive Neuroscience | Molecular and Cellular Neuroscience
Extensive serotonin (5-HT) innervation throughout the brain corroborates 5-HT’s modulatory role in numerous cognitive activities. 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 (Nrxn) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in Nrxn genes are associated with neurodevelopmental disorders including ASD. However, the role of Nrxn genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three Nrxn genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of Nrxns in 5-HT neurons impaired 5-HT release in the dorsal raphe nucleus and dorsal hippocampus and decreased serotonin transporter distribution in specific brain areas. Furthermore, 5-HT neuron-specific Nrxn knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission and the execution of complex behaviors.
Neuroscience, serotonin, autism spectrum disorder, Neurexin
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DOI of Published Version
bioRxiv 2021.12.09.471904; doi: https://doi.org/10.1101/2021.12.09.471904. Link to preprint on bioRxiv.
Cheung A, Matsui A, Abe M, Sakimura K, Sasaoka T, Uemura T, Kawasawa YI, Futai K. (2021). Neurexins in serotonergic neurons regulate serotonin transmission and complex mouse behaviors [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.12.09.471904. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2213
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