Early life adversity enhances prosocial helping towards a cagemate and reshapes brain-wide neural activity and network organization

Early life adversity (ELA) is linked to changes in social behavior and emotional regulation and to increased risk for developing mood and conduct disorders. However, the effects of ELA on empathy and its associated behaviors, including prosocial helping, remain poorly understood. Animal models of ELA provide a tractable way to study how early rearing conditions impact prosocial behavior and underlying neural circuitry. In the current study, adult male and female rats reared under maternal separation (MS) or control conditions were tested in a helping behavior task in which they could release a trapped cagemate. Behavior was assessed across repeated testing sessions and brain-wide neural activity was quantified using c-Fos on the final test day. Contrary to our hypothesis, we found that MS-reared rats showed more consistent helping behavior, with shorter latencies to help on average, compared to control-reared animals. In addition, MS-reared rats displayed increased social play following release. At the neural level, MS-reared rats displayed more c-Fos expression across multiple brain regions, including prefrontal, amygdala, sensory, and striatal regions involved in motivation and social decision making. Network analyses further revealed altered functional connectivity in ELA-reared animals, with heightened connectivity in stress-related regions such as the lateral habenula. Together, these findings demonstrate that ELA impacts prosocial helping behavior and is associated with widespread changes in neural activity and network organization. This work provides insight into how early adversity shapes social motivation and the neural systems supporting prosocial behaviors.