Empathy, the capacity for shared emotional valence with others, allows for cooperativity and social bonding between individuals. The evolutionary basis of the empathic behaviors observed across numerous species can be described using the Perception Action Model (PAM), in which shared affect can promote an action that eliminates the distress of both the Target and, by extension, the Observer . However, clinical studies indicate empathy is dysregulated in neuropsychiatric disorders like autism and addiction, which makes the elucidation of underlying behavioral, affective, and neurobiological variables of empathy paramount. We first introduce and validate a novel model of targeted helping, in which rats learn to aid a distressed conspecific in the absence of social reward. Next, using this model, we identify sex differences in sensory and affective signaling, including the impact of direct visualization of a distressed conspecific, and the type of ultrasonic vocalizations (USV) made between animal pairs, during the task. Further, neuronal activity in cortical and subcortical regions of interest showed distinct sex-specific patterning across time during targeted helping. Finally, we directly examined the effect of the anterior insula, a region active during perspective taking and emotional regulation hypothesized to be a critical node in the empathic brain, during empathic behavior. We not only confirmed that the anterior insula was activated during the task, but inhibition of the insula, both pharmacologically and chemogenetically, significantly attenuated helping behavior. Further, tracer studies were performed in order to elucidate critical insula-specific circuits that may modulate targeted helping. These studies, using a newly validated model of targeted helping, work to inform the underlying affective and biological variables that modulate empathic behavior in the hopes of improving the treatment outcomes and quality of life of those diagnosed with neuropsychiatric disorders
