Autism spectrum disorder (ASD) is associated with neurodevelopmental alterations, including atypical forebrain cellular organization. Mutations in several ASD-related genes often result in cerebral cortical anomalies, such as the abnormal developmental migration of excitatory pyramidal cells and the malformation of inhibitory neuronal circuitry. Notably here, mutations in the CNTNAP2 gene result in ectopic superficial cortical neurons stalled in lower cortical layers and alterations to the balance of cortical excitation and inhibition. However, the broader circuit-level implications of these findings have not been previously investigated. Therefore, we assessed whether ectopic cortical neurons in CNTNAP2 mutant mice form aberrant connections with higher-order thalamic nuclei, potentially accounting for some autistic behaviors, such as repetitive and hyperactive behaviors. Furthermore, we assessed whether the development of parvalbumin-positive (PV) cortical interneurons and their specialized matrix support structures, called perineuronal nets (PNNs), were altered in these mutant mice. We found alterations in both ectopic neuronal connectivity and in the development of PNNs, PV neurons and PNNs enwrapping PV neurons in various sensory cortical regions and at different postnatal ages in the CNTNAP2 mutant mice, which likely lead to some of the cortical excitation/inhibition (E/I) imbalance associated with ASD. These findings suggest neuroanatomical alterations in cortical regions that underlie the emergence of ASD-related behaviors in this mouse model of the disorder.

The central auditory system integrates signals received from both ears to derive information about the spatial and spectral features of the emitting sound source. This binaural processing of acoustic information is critical for both communication and environmental awareness. However, these binaural computations may become disrupted in individuals diagnosed with autism spectrum disorder (ASD), potentially leading to difficulties with speech perception, sound attention, and sensory hypersensitivity. Here, we present a narrative review of the emerging evidence regarding binaural processing deficits in ASD. These deficits include elevated thresholds for interaural time and level differences and reduced sound localization accuracy. In addition, physiological data suggests that these behavioral traits correspond with abnormal activity in central auditory structures. Molecular and cellular alterations to central auditory circuits may underlie these behavioral and physiological features, which could arise from both genetic and environmental factors. Overall, binaural processing alterations in ASD remain under-studied, with a need for future studies to identify neural circuit-level mechanisms and potential interventions.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by differences in social communication and restricted, repetitive patterns of behavior