Insular input to the prelimbic cortex underlies social affective behavior in rats

Abstract To navigate social interactions, animals must adjust their behavior in response to information derived from conspecifics. The integration of social information and coordination of behavior occurs within a distributed social decision making network. The prelimbic (PL) prefrontal cortex and the insula (IC) are key nodes in the salience network which is anatomically situated to interact with the social brain. We investigated the IC-PL circuit in a social affective preference (SAP) test in which subject rats are exposed to 2 age-matched conspecifics where one is stressed via footshock and the other is naive to stress. Typically, rats approach stressed juvenile conspecifics but avoid stressed adults. Using a combination of local and tract specific loss of function methods, we demonstrate that the PL, anterior IC, and the tracts between the posterior or anterior IC and the PL are necessary when rats face the choice to approach or avoid stressed conspecifics. Going further, chemogenetic inhibition of PL neurons innervated by the IC also interfered with social affective behaviors. These studies enrich our understanding of the neurobiology of social decision making by establishing a mechanistic link between insular and prefrontal circuits. Significance Statement The successful navigation of social interactions requires detection of the emotional states of others and the appropriate behavioral output. While the insula and prefrontal cortex have both been implicated as key brain regions in social decision-making and the salience network, their functional role in guiding social behaviors are largely unknown. Using a combination of region-specific and circuit manipulations in rats, we present evidence of the necessity of the insula-prefrontal pathway in the approach and avoidance of stressed others, reinforcing the importance of this cortical system in social affective processing. This work provides new insight into the network-level mechanisms underlying social behavior and highlights an important circuit that may be relevant to understanding neuropsychiatric disorders with social impairments.