Early exposure to male intruders induces precocious activation of fear-related neural circuits in a sex-specific manner in rat pups.

The early exposure of mother-litter dyads to adult male intruders in the home cage leads to the precocious expression of fear responses in rat pups when confronted with an intruder during the stress-hyporesponsive period (SHRP). As fear-related circuits are still maturing during this period in a sex dependent manner, this study investigated whether this early-life experience promotes the activation of fear-related circuits in 8-day-old female and male pups confronted with an adult male. As expected, pups exposed to male intruders from postnatal days (PND) 1-4 exhibited increased immobility and reduced ultrasonic vocalizations when subsequently tested with an adult male on PND 8, and this response did not differ from that displayed by pups outside the SHRP (PND 14). Fear behavior was accompanied by an increase of c-Fos expression in key areas implicated in fear processing, including the amygdala (medial, cortical, basomedial, basolateral nuclei), paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus in 8- and 14-day old pups. However, neural activation patterns differed between sexes, suggesting sex-specific maturational trajectories influenced by the exposure of the dyad to the male intruder. These findings demonstrate that an early social context that alters the mother's behavior induces the precocious activation of fear-related circuits in male and female pups, highlighting the sensitivity of emotional neural circuits to maternal and environmental influences during the neonatal period.