Agouti integrates environmental information to regulate natural variation in paternal behavior

Male investment in offspring rearing through paternal care is rare among mammals and the neural mechanisms governing its emergence are poorly understood. We leveraged the natural paternal behavior of African striped mice (Rhabdomys pumilio) in combination with brain-wide cFos quantification, single-nucleus RNA-sequencing, viral-mediated gene manipulation, and environmental manipulation to dissect the neural basis of natural variation in male parenting. We find that socio-environmental conditions drive individual variation in male alloparenting such that post-weaning social isolation increases paternal care while social living in higher density groups increases infanticide. This natural variation in care corresponds to neural activity in the medial preoptic area and changes in correlated activity across brain regions. Within the medial preoptic area, expression of agouti signaling protein (Agouti) in neurons is increased by group housing and is negatively associated with care, and overexpression of Agouti reduces care and enhances infanticide in previously tolerant animals. Naturalistic manipulations further reveal that Agouti integrates long-term housing conditions rather than food availability/hunger. Together, our results demonstrate that Agouti acts as a molecular integrator of socio-environmental information to drive variation in paternal care.