Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Several genetic causes of ASD have been identified and this has enabled researchers to construct mouse models. Mouse behavioral tests reveal impaired social interaction and communication, as well as increased repetitive behavior and behavioral inflexibility in these mice, which correspond to core behavioral deficits observed in individuals with ASD. However, the connection between these behavioral abnormalities and the underlying dysregulation in neuronal circuits and synaptic function is poorly understood. Moreover, different components of the ASD phenotype may be linked to dysfunction in different brain regions, making it even more challenging to chart the pathophysiological mechanisms involved in ASD. Here we summarize the research on mouse models of ASD and their contribution to understanding pathophysiological mechanisms. Specifically, we emphasize abnormal serotonin production and regulation, as well as the disruption in circadian rhythms and sleep that are observed in a subset of ASD, and propose that spatiotemporal disturbances in brainstem development may be a primary cause of ASD that propagates towards the cerebral cortex.
Keywords: 3-chamber test; ASD biology; Autism; Autism spectrum disorder; Behavior; Brainstem; CNV; Circadian rhythm; Dorsal raphe nuclei; Hindbrain; Mouse model; Neurodevelopmental disorder; PI3K-mTOR; Serotonin; Sleep; Social behavior; Somatosensory; Suprachiasmatic nucleus; Synapse; Ultrasonic vocalization.
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