Dual circuits originating from the ventral hippocampus independently facilitate affective empathy

Affective empathy enables social mammals to learn and transfer emotion to conspecifics, but an understanding of the neural circuitry and genetics underlying affective empathy is still very limited. Here, using the naive observational fear between cagemates as a paradigm similar to human affective empathy and chemo/optogenetic neuroactivity manipulation in mouse brain, we investigate the roles of multiple brain regions in mouse affective empathy. Remarkably, two neural circuits originating from the ventral hippocampus, previously unknown to function in empathy, are revealed to regulate naive observational fear. One is from ventral hippocampal pyramidal neurons to lateral septum GABAergic neurons, and the other is from ventral hippocampus pyramidal neurons to nucleus accumbens dopamine-receptor-expressing neurons. Furthermore, we identify the naive observational-fear-encoding neurons in the ventral hippocampus. Our findings highlight the potentially diverse regulatory pathways of empathy in social animals, shedding light on the mechanisms underlying empathy circuity and its disorders. [Display omitted] •Ventral hippocampus (vHPC) encodes observational fear (OF) neurons toward familiar companions•vHPC OF neurons disinhibit downstream lateral septum (LS) GABAergic neurons in OF•Dual neural circuits from vHPC to NAc and LS-BLA independently regulate OF Peng et al. have discovered functionally independent dual neural circuits, including the neurons in the ventral hippocampus (vHPC), nucleus accumbens, lateral septum, and basolateral amygdala, that regulate the affective empathy between mice. They also classified the neurons in the vHPC that encode observational fear.