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

> **NIH NIH R00** · DUKE UNIVERSITY · 2020 · $245,321

## Abstract

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.

## Key facts

- **NIH application ID:** 9974569
- **Project number:** 5R00MH115165-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Jenna Ann McHenry
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,321
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974569

## Citation

> US National Institutes of Health, RePORTER application 9974569, Dissecting midbrain and preoptic circuits that regulate social and nonsocial emotional states (5R00MH115165-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974569. Licensed CC0.

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