Human studies demonstrate that women outperform men in standard tests of empathy. Recent data also suggest that women to a higher degree recruit mirror neuron-containing areas, which have been linked to processing of social emotional stimuli. However, it is not clear whether these differences are due to sex-specific mechanisms of empathy. Empathy, which in its simplest form can be defined as the capacity to be affected by the emotional state of a conspecific, is vital for survival, as it allows individuals to learn about potential danger from other members of their social group and thereby to adapt rapidly to environmental challenges. Viewed in this way, empathy is not a phenomenon limited to higher primates. With a goal of studying neural mechanisms of empathy, we have designed an animal model, in which a naive rat interacts with its cagemate, which was subjected to fear conditioning. We used this model of socially transferred fear to compare behavioral responses and pattern of neuronal activation in male and female rats. As multiple behavioral and molecular measures in females depend on current sex hormone levels, we also chose to monitor estrus cycle phase. We found that a brief interaction with a cagemate subjected to fear conditioning results in a robust activation of both medial and lateral divisions of central nucleus, as well as lateral and cortical nuclei of the amygdala and the prelimbic cortex in male rats. In female rats we found marked differences in c-Fos expression between estrus and diestrus. In diestrus, the activation patterns partially reflected the expression observed in males, whereas in estrus there were no significant differences between experimental groups. Collectively, our results support the existence of a neural circuit processing empathy. Moreover, our data show sex- and estrus cycle phase- specific activation patterns within the limbic system.
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