Neuroendocrine mechanisms underlying paternal experience-induced plasticity of the hippocampus

Evidence suggests that males, like females, undergo altered structure and function of the hippocampus postpartum, a brain region that regulates certain aspects of emotion, learning, and memory. These behaviors are beneficial for successful parenting. In maternal rodents, offspring contact contributes to postpartum hippocampal plasticity in both mothers and offspring. Fathers do not undergo pregnancy, parturition, or lactation, therefore, the impact of offspring on hippocampal plasticity is less clear. California mouse (Peromyscus californicus) fathers are highly paternal, making this monogamous species a good model of paternal care. In this species, between postnatal days 15 and 21 paternal behavior becomes more active (i.e. increased pup retrievals) to care for pups that are beginning to explore outside of the nest. I observed reduced anxiety-like behavior in fathers specifically within this temporal window. Concomitant with attenuated anxiety-like behavior, I found that fathers maintain survival of adult born neurons in the dentate gyrus of the hippocampus. Enhanced hippocampal plasticity is not restricted to adult neurogenesis, as dendritic spine density in the dentate gyrus is increased in fathers at this same time – an effect that lasts until weaning. When permanently separated from their offspring, fathers show increased passive stress coping and reduced spine density in the DG. Taken together, these data suggest that the degree of active father-offspring interaction significantly alters hippocampal plasticity in the father. Estradiol and its receptors have been implicated in alterations to anxiety and adult neurogenesis in both males and females. I observed that estrogen receptor β (Erβ) mRNA expression was elevated in whole hippocampal homogenates at PND 16 in fathers. Similarly, circulating estradiol was elevated at both PND 2 and PND 16. After inhibition of Erβ with the drug tamoxifen, the number of surviving adult born neurons was suppressed in fathers alone. Taken together, these data suggest that in fathers, hippocampal plasticity occurs concomitantly with active father-offspring contact and that this plasticity, at least structural, is driven by activation of Erβ. Understanding paternal experience-induced plasticity and the mechanisms that drive it, may help to prevent deficits in paternal behavior that can disrupt offspring development and contribute to emotional dysregulation in fathers