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Neural Mechanisms of Pup-Affiliative Behavior in Adult Virgin California Mice (Peromyscus californicus)

Abstract

In biparental species, in which both parents care for their offspring, the neural mechanisms underlying the initiation of paternal care are not well understood. The neural mediators of paternal behavior overlap substantially with those underlying maternal behavior; however, few studies have looked at the functional roles of classical neurotransmitter systems, such as norepinephrine (NE), in the initiation of paternal care. Moreover, the cellular and molecular mechanisms that govern neural plasticity during the transition to parenthood remain largely unexplored. To address this gap, studies in this dissertation examined the role of NE in the onset of paternal behavior, as well as the mechanisms underlying neural plasticity resulting from experience with pups in adult California mice (Peromyscus californicus), a biparental species. These experiments mainly focused on adult virgins, as I was interested in examining the neural mechanisms underlying the initiation of pup-affiliative behavior in this species. The first study investigated the effects of nepicastat, an inhibitor of NE synthesis, on pup-directed behavior in adult virgin California mice. I found that nepicastat significantly reduced the number of virgin males and females that approached an experimentally presented pup and that displayed parental behavior. In the second study, I examined the effects of nepicastat on neural activation, as indicated by c-Fos expression, in brain regions associated with parental care and anxiety following exposure to pups. Virgin males injected with nepicastat exhibited significantly reduced neural activation in the medial amygdala following pup exposure compared to vehicle-injected controls. Finally, I examined the impact of exposure to pups on perineuronal net expression (PNN) in the brains of male and female California mice. PNNs are extracellular matrix structures that are known to influence synaptic plasticity. I used a pup sensitization paradigm that promotes the onset of paternal behavior in virgin California mice. I found that dynamic changes in PNN expression in the brain occur with repeated exposure to pups in male but not female California mice. These findings provide insights into the role of the noradrenergic system in the onset of parental behavior as well as the mechanisms regulating neuroplasticity of the paternal brain during the transition to parenthood.

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