Heightened empathic responses led by imbalanced cortico-amygdala circuit in Shank3 autism mouse model

Affective empathy is defined as individual percept and respond to another emotion appropriately, an essential building block for human society. Historically, aberrant empathy was considered as major characteristics of autistic individuals but recently it has been challenged. It required mechanistic understanding of the empathy process, especially how autistic individual percept other emotion. By evaluating the social fear transfer response, we reported a critical role of Shank3 gene, one of the most replicated causative autism genes, in cortico-amygdala circuit in balancing and integrating affective empathy process using preclinical mouse models. We found that Shank3 complete deletion mouse model exhibited unexpected exaggerated affective responses, which was encoded by defective neural dynamics of Shank3-deficient cingulate projecting amygdala circuit. This work for the first time showcased an interplay between gene and affective empathy responses in mouse and laid the groundwork for modeling empathy in autism and other neuropsychiatric disease.