Male caregiving experience alters hippocampal neuroplasticity and transcription independent of reproduction in a biparental species.

In mammals, measurable changes in brain and behavior accompany the transition to parenthood. In the biparental California mouse, Peromyscus californicus, fathers experience enhanced neuroplasticity, including increased hippocampal dendritic spine density, reduced anxiety, and improved memory. Here, we first investigate whether siring offspring or pup interaction drives structural neuroplasticity in fathers and find that hippocampal spine density is positively associated with caregiving experience, even in the absence of reproduction. Next, we evaluate the transcriptional response to caregiving in the hippocampus of these males and identify 158 differentially expressed genes between fathers and non-fathers, many of which are associated with neurogenesis, neuronal signaling, and dendritic plasticity. Importantly, 11 of the differentially expressed genes in fathers are similarly regulated in non-fathers that interacted with unrelated pups, suggesting that even limited interaction with pups, in the absence of siring a litter, can induce transcriptional changes in the male brain. Moreover, of the differentially expressed genes that encode for transcription factors and cofactors, we repeatedly find that their expression correlates with spine density in males with varied caregiving experience, thus linking these transcriptional changes to neuroplasticity. Together, this work demonstrates that caregiving-regardless of whether the pups are the male's own biological offspring-drives hippocampal neuroplasticity and transcriptional changes in males of a biparental species.