Oxytocin-immunoreactive cells in the paraventricular nucleus of the hypothalamus

How do hormonal changes that happen during pregnancy and birth change the brain? Are these changes associated with changes in behavior?

Pregnancy and the postpartum period is a time of profound changes in both hormones and behavior in females. While some changes in behavior (e.g., bonding, displaying maternal behaviors) are adaptive, other behavioral changes are indicative of anxiety or depression. This is significant, as an estimated 15-20% of women experience postpartum depression and/or anxiety following childbirth. Although it is assumed that hormonal changes associated with pregnancy and birth are related to the symptoms of postpartum depression and anxiety, how these hormonal changes impact the brain is poorly understood. Using animal models, we can isolate and manipulate these hormonal changes to ask whether they influence changes in the brain and in behavior. Ongoing experiments in my lab are looking at peripartum plasticity in oxytocin and dopamine signaling and the resulting impact on behavioral indices of anxiety and depression. A better fundamental understanding of these processes is vital to understanding the neurobiological components of postpartum depression/anxiety, and may point to new therapeutic targets in people.

How does sex experience change the brain? Are these changes the same in males and females?

One of my overarching research interests is understanding the neurobiology of naturally-motivated behaviors. Specifically, I am interested in the effects of rewarding experiences on future behavior, focusing on how rewarding experiences that occur as part of an individual’s everyday life can lead to long-lasting changes in the brain. To that end, I use sex behavior in Syrian hamsters as a model to investigate the neurobiological mechanisms of natural reward and brain plasticity following rewarding experiences. Given that naturally-motivated behaviors are driven by the same neural circuitry as synthetically-motivated behaviors (e.g., taking drugs of abuse), it is reasonable to assume that understanding the how the brain processes natural rewards has important implications for understanding pathologies of motivation.

Previous research has demonstrated that sex experience increases the density of dendritic spines on neurons of the nucleus accumbens, a brain region critical for reward and motivation. Put another way, sex experience changes the physical structure of neurons in the nucleus accumbens, making it possible for more synapses form. Although this has been shown to occur in both males and females of several species, and has important implications for the response to future rewarding experience (either natural or synthetic), the molecular events that lead to this structural plasticity are not known. Furthermore, whether the same signaling mechanisms mediate this change in both sexes are not known. In my lab, we are using molecular biology and behavioral pharmacology techniques to try to dissect the neural mechanisms underlying this neuroplasticity.

What are the neural mechanisms of sexual attraction/copulation? Are these circuits susceptible to plasticity?

My doctoral research used excitotoxic micro-lesions and neuroanatomical tract tracing to investigate the neural circuitry underlying appetitive and consummatory aspects of reproductive behavior in male hamsters. Specifically, I demonstrated that the connections between the medial amygdala and medial preoptic area (MPOA) are necessary for copulation, but not attraction; in contrast, the connections between the medial amygdala and bed nucleus of the stria terminalis (BNST) are necessary for attraction, but not copulation. Interestingly, giving animals sexual experience prior to lesioning the BNST or MPOA ameliorated the behavioral effects of the lesions, suggesting that sexual experience can mitigate the necessity of these brain areas for producing reproductive behaviors. The mechanism of this plasticity is unknown. Ongoing experiments in my lab are testing the hypothesis that plasticity following sex experience is mediated by increased connectivity between the BNST/MPOA and the nucleus accumbens.