CARDIAC INTEROCEPTION AND INSULAR CORTEX: A PATHWAY TO UNDERSTANDING SOCIAL DEFICITS IN AUTISM

Interoception enables the brain to monitor internal bodily states and adapt behavior accordingly. The posterior insular cortex (pIC) plays a central role in integrating interoceptive and sensory information, yet its contribution to negative social experiences remains poorly understood. This gap is particularly relevant for autism spectrum disorder (ASD), where altered sensory integration and social behavior co-occur.
Here, we investigate how brain–heart communication supports behavioral responses to negative social encounters, using Shank3-deficient mice as a model of ASD and wild-type controls. We focus on social behaviors with negative valence, which remain unexplored in ASD research. By combining behavioral assays with fiber photometry, miniscope imaging, and cardiac telemetry, we monitor neuronal activity in the pIC and cardiac dynamics during baseline and social interactions.
Shank3-deficient mice display altered aggressive behavioral organization despite preserved total engagement time. In wild-type animals, aggressive encounters elicit coordinated changes in pIC activity and heart rate. In contrast, Shank3-deficient mice show reduced synchrony between cardiac signals and pIC activity during negative social events. To assess the circuit basis of this dissociation, we examine the contribution of distinct behavior-specific neuronal populations within the pIC. Parallel functional and structural analyses of the heart indicate that loss of Shank3 alters cardiac properties that may impair brain–heart integration.
Together, these findings suggest that Shank3 loss leads to maladaptive responses to negative social encounters by disrupting the integration of cardiac signals with interoceptive cortical circuits. This work highlights brain–heart communication as a key mechanism linking interoception, social behavior, and ASD-related phenotypes.