Modulation of social valence by insular cortex activity during acute social isolation in mice

For social animals, social isolation is a potential threat to survival, and therefore can be considered innately aversive. Long-term social isolation induces a variety of social and affective deficits and has been used as a stress model in animal studies, with increasing insight into its underlying neural mechanisms. In contrast, short-term social isolation is known to elicit prosocial behaviors such as rebound social interactions, yet the neural basis of these adaptive responses remains poorly understood. Here, we investigated the effects of short-term social isolation on social and appetitive behaviors and examined the role of the insular cortex in modulating social preference in male mice. Three days of social isolation increased social contacts in a three-chamber social preference test. Additionally, socially isolated mice showed higher food intake in the home cage compared with the group-housed mice, and those exhibiting a higher social preference following social isolation also tended to consume more food during the isolation, postulating a potential correlation of social craving and food craving. Furthermore, chemogenetic suppression of the insular cortex during social isolation reduced rebound social interactions. We propose that the insular cortex modulates social valence by serving as an alert center for social deprivation. Our findings may help advance understanding of the neuronal mechanisms that underlie adaptive social and appetitive behaviors in response to social isolation.