Environment tunes male caregiving via Agouti signaling in the hypothalamus
In African striped mice, postweaning social isolation increases male alloparental care while high-density group housing raises infanticide. Brain activity in the medial preoptic area (MPOA) correlates with care variation, and Agouti signaling protein (ASIP) expression is higher in infanticidal males and negatively linked to caregiving. Causally, overexpressing Agouti in the MPOA suppresses paternal care and promotes infanticide, implicating ASIP acting on MC4R receptors to gate caregiving. SnRNA-seq shows Agouti is differentially enriched across MPOA neuron types, not due to changes in cell composition, and Agouti integrates long-term socio-environmental cues rather than hunger. Overall, paternal care relies on conserved maternal/paternal circuits, with Agouti as an environmental switch that biases these circuits toward care or aggression through melanocortin signaling.