Ventral striatal neuroimmune signalling biases the expression of social memory in male mice.

Social behaviours are highly sensitive to inflammatory states. However, the precise contribution of neuroinflammation in the ventral striatum to social memory remains unclear. Using a mouse model of recurrent herpes simplex virus-1 (HSV-1) infection and a complementary model of region-restricted inflammation induced by bilateral intra-ventral striatum lipopolysaccharide (LPS) injection, we show that ventral striatal inflammation impacts social memory expression. Both HSV-1-infected and LPS-treated mice failed to discriminate between old and novel conspecifics, with LPS-treated animals showing a slight preference for the known stimulus. In these animals, social memory alterations were associated with microglial activation, inflammatory signalling, and increased GluA2 expression in the ventral striatum and were not dependent on altered social novelty sensitivity. In both models, behavioural alterations were rescued by dexamethasone treatment. Finally, LPS-induced neuroinflammatory markers in the ventral striatum correlated with preference for the familiar social stimulus. Together, these findings identify ventral striatal inflammation as a key modulator of social memory expression.