Although it is well known that paternal behavior may be of equal importance as maternal behavior for the physical and psychological well-being of adult partners and their children, our knowledge about the neurobiology of parental behavior is almost exclusively derived from studies of maternal behavior. The scarcity of knowledge on the neurobiology of paternal behavior is primarily due to a lack of appropriate animal models. In recent years, the socially monogamous prairie vole (Microtus ochrogaster) has emerged as a useful animal model for the study of complex social behaviors, including pair bonding between adults and bi-parental care towards offspring [1]. A critical aspect of all behaviors is the epigenetic underpinnings that may influence them. Environmental factors, including social interactions, have profound effects on one?s physiological and behavioral functions. A growing body of evidence has indicated that epigenetic mechanisms can encode these environmental factors in the brain and shape behavior. Social interactions, such as maternal [2], sexual [3], and social defeat [4] experience can affect animal behavior via epigenetic regulations. In prairie voles, treatment with histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) or sodium butyrate (SB), or mating increased oxytocin receptor (oxtr) and vasopressin V1a receptor (avpr1a) gene expression in the nucleus accumbens (NAcc), which occurred through histone acetylation at the oxtr and avpr1a promoters and facilitated social bonding [5, 6]. These data demonstrate the utility of the prairie vole as a model to study epigenetic regulation of social behaviors. In this application, we propose to use male prairie voles as an animal model to test the hypothesis that the HDAC inhibitors facilitate epigenetic regulation of paternal behavior by enhancing neurochemical receptor expression. We will compare male voles that receive intracerebroventricular (icv) injections of vehicle (cerebrospinal fluid: CSF) containing different concentrations of HDAC inhibitors, TSA or SB, in order to reveal the effective dose of the HDAC inhibitors that may enhance paternal behavior. We will then measure global acetylated and unmodified histones, neurochemical receptors (including oxytocin, dopamine, and vasopressin), and TSA- or SB-enhanced histone acetylation at the promoter regions of these receptors in select brain areas important for social behaviors. These data will illustrate the specific gene(s) in brain area(s) whose transcription is enhanced by HDAC inhibitors. Thereafter, we will administer TSA or SB into the brain region, with or without the receptor antagonist, to examine its effect on paternal behavior. Together, these data will shed light on the neurochemicals and brain circuitry important for the epigenetic regulation of male parental behavior ? a scientific question with high translational value for human health.
Paternal behavior plays an important role for the physical and psychological well-being of the adults involved, as well as the development and health of the child. Here, we propose to examine how central administration of the HDAC inhibitors affects paternal behavior by facilitating specific neurochemical receptor expression through histone acetylation in the brain of the socially monogamous male prairie voles, which will establish a solid foundation for further investigation of epigenetic regulation of paternal behavior.
