Sexually dimorphic control of affective state processing and empathic behaviors

Recognizing the affective states of social counterparts and responding appropriately fosters successful social interactions. However, little is known about how the affective states are expressed and perceived and how they influence social decisions. Here, we show that male and female mice emit distinct olfactory cues after experiencing distress. These cues activate distinct neural circuits in the piriform cortex (PiC) and evoke sexually dimorphic empathic behaviors in observers. Specifically, the PiC → PrL pathway is activated in female observers, inducing a social preference for the distressed counterpart. Conversely, the PiC → MeA pathway is activated in male observers, evoking excessive self-grooming behaviors. These pathways originate from non-overlapping PiC neuron populations with distinct gene expression signatures regulated by transcription factors and sex hormones. Our study unveils how internal states of social counterparts are processed through sexually dimorphic mechanisms at the molecular, cellular, and circuit levels and offers insights into the neural mechanisms underpinning sex differences in higher brain functions. [Display omitted] •Male and female mice display different empathic behaviors in response to others’ pain•Female mice show social preference, whereas male mice display excessive self-grooming•Distinct behaviors arise from neural circuits involving two populations of PiC neurons•The two PiC neuron populations exhibit distinct gene expression signatures Fang et al. discovered that male and female mice display different empathic behaviors in response to others’ pain. Specifically, males engage in self-grooming, whereas females demonstrate social approaching. Processing information about others’ pain involves distinct neural circuits for each sex. Importantly, these circuits inherently differ in gene expression patterns.