Dissecting midbrain and preoptic circuits that regulate social and nonsocial emotional states

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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.