Social rejection following neonatal inflammation is mediated by olfactory scent cues.

Early-life exposure to inflammation has been associated with several behavioral and cognitive deficits detected in adulthood. However, early behavioral changes have not been well described in rodent models of infection, specifically with respect to social behavior. In the present work we show that lipopolysaccharide (LPS) challenge at 3 and 5days of age reduced overall social contact time in male juvenile rats, primarily mediated by the amount of contact they received from a novel conspecific. Given that there are important sensory, motor, and motivational components that underlie social interaction we sought to uncover the mechanism(s) responsible for the reduced social contact directed towards neonatal (n)LPS treated animals. Using an intranasal perfusion procedure, we induced a ZnSO4 lesion in a subset of novel conspecifics, effectively disrupting their olfactory processing via olfactory neuroepithelium degeneration. Overall, this procedure equalized the amount of social contact directed towards nLPS animals compared to nsaline rats. To determine whether nLPS disrupted auditory communication we evaluated ultrasonic vocalizations (USVs) for the total number and duration of calls, and the average duration and frequency from each vocalization recording. There were no differences in USVs across treatment groups. Treating nLPS rats with diazepam maintained the level of social contact they initiated, compared to the stress-induced decrease observed in their saline treated counterparts. However, diazepam did not stabilize the amount of contact directed towards them. Together, this indicates that neither vocalized motor pathways nor anxiety cues, mediated by auditory/motor communication, are involved in the social deficits following nLPS. Instead, our data suggest that olfactory indicators, likely mediated through microbiota/immunomodulatory scent signals underlie the reductions in social contact that follow neonatal inflammation.