Jenna A. McHenry, Ph.D. - US grants

Mating is a socially rewarding experience that may exert protective benefits to health and fitness and buffers against the deleterious effects of stress across a number of mammalian and non-mammalian species. However, the neurobiological mechanisms that underlie these effects are poorly understood, and studies inclusive of female subjects are extremely limited. Using both male and female rodent models, the investigators will utilize a combination of behavioral, cellular, and neurochemical studies to better understand the impact of mating history on stress-related systems. In-vivo neurochemical studies will also allow for the collection and analysis of neurotransmitter release in awake and behaving animals during mating and a stressful encounter. Mating history is expected to dampen stress reactivity through neurochemical changes in regions of the brain that differ between males and females, and differences may be observed between males and females. The evolutionary advantage for the anxiety-reducing, stress-buffering, and rewarding aspects of mating may be to increase an animal's willingness to explore new environments to search for mating partners, and thus facilitate reproduction and ultimately pass on its genes. This research will advance a broader scientific field that includes our understanding of differences between males and females and similarities in the behavioral and neurobiological systems regulating stress and reproduction and how these systems interact. In addition, it will have a broader impact on a number of undergraduates who are trained in neuroscience research in this lab. These students currently include members of groups traditionally underrepresented in science. Further, the investigators will talk to K-12 students about the dissertation research and teach basic neuroscience through outreach activities including Brain Awareness Week and the North Florida Brain Bee, to promote scientific interest in the local community.

Dysregulated social and emotional processing is a debilitating issue across a wide range of neuropsychiatric disorders, including anxiety disorders, major depression, schizophrenia, and autism spectrum disorders. These disorders not only have severe impacts on individual well being but also represent a tremendous economic burden on the U.S. Since social and emotional disruptions often co-occur, a key question is how social processing neurons are intertwined with or embedded in positive and negative valence systems. This interplay is likely important to link social contexts with emotional representations and promote motivation. However, the precise functional neural circuitry that orchestrates these complex interactions remains unresolved and it is unclear whether social and nonsocial emotional information is processed through overlapping or distinct pathways. Recent technological developments have made it possible to combine calcium imaging and miniature epifluorescence microscopes to visualize the natural activity dynamics of individual neurons with anatomical and molecular precision, on a large scale in freely behaving animals. The goal of this proposed K99/R00 research is to use these approaches, in conjunction with in vivo optogenetic strategies, to chronically monitor and acutely manipulate the activity of precise neural circuits during social and nonsocial behaviors in mice. In particular, this project will focus on circuitry that connects the medial preoptic area (mPOA), an essential site for social behavior across mammals, with midbrain dopaminergic neurons that regulate motivational states. Activity-dependent monosynaptic tracing and combined optogenetic imaging approaches will also elucidate how salient sensory cues are transmitted to mPOA-midbrain circuits to adjust social and emotional states. Completion of the proposed aims is expected to be impactful because these studies will illuminate the causal and natural neural dynamics that underlie social and nonsocial emotional behavior. While the mesolimbic dopamine system has been well implicated in adaptive and maladaptive reward processing, it is unknown whether social motivation deficits are due to perturbations in specialized social pathways or due to more generalized reward disruptions. Identifying how these processes interact at the individual neuron level is of critical importance because without this information, we are unlikely to discover the ways in which certain social and nonsocial behavioral abnormalities arise. This career development award will provide the candidate with the technical training, conceptual background, and mentorship from renowned experts within the field. Ultimately, this training will uniquely position this young investigator to transition to an independent research program focused on investigating social and nonsocial emotional deficits that are common to many mental health disorders.