# VTA-nucleus accumbens circuit dynamics underlying stress susceptibility

> **NIH NIH K08** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2020 · $196,957

## Abstract

Project Summary
I am an MD-PhD psychiatrist with the intertwined interests of understanding the neural basis of behavior and
treating psychiatric patients. My goal is to become an expert on the circuit level mechanisms of neural
transmission underlying stress, resilience and affective disorders. I plan to direct a research laboratory at an
academic medical center, studying the neurophysiology of stress and affect, and have a small clinical practice.
For my training, I moved to the New York State Psychiatric Institute (NYSPI). The NYSPI is the primary
component of the Psychiatry Department of Columbia University, and is one of the largest mental health
research facilities in the world. It has state-of-the-art facilities and a broad range of world-class scientists.
At Columbia, I joined the laboratory of Dr. Joshua Gordon, an expert at studying circuits underlying psychiatric
disorders. I also enlisted the mentorship of Dr. Eric Nestler, a pioneer in the field of chronic stress. With their
guidance and this grant, I hope to accomplish 3 objectives: 1) Integrate in vivo circuit and behavioral analyses,
2) Learn to modulate circuits with optogenetics, 3) Develop as an independent physician-scientist.
Depression is the leading cause of disease burden in the United States. Many patients never recover despite
extensive treatment. Stress can precipitate depression yet some people are remarkably resilient in the face of
adversity. Moreover, although women develop depression at nearly twice the rate of men, the vast majority of
research on the physiology of stress susceptibility has been conducted in male subjects. Understanding how
neural circuits function in susceptibility and resilience to stress is an exciting new approach to developing
antidepressant treatment. The goal of my proposal is to identify how communication between the ventral
tegmental area (VTA) and the nucleus accumbens (NAc), areas that process both reward and stress,
contribute to susceptibility and resilience in males and females. The VTA-NAc circuit undergoes substantial
molecular and electrical changes in mice that develop depression-like symptoms in response to stress.
However, it remains unknown how these changes impact circuit communication. In Aim 1, I propose to record
VTA-NAc circuit communication of susceptible and resilient male and female mice before, during and after
undergoing chronic stress. Three different cell-types in the VTA project to the NAc and these projections may
uniquely contribute to the development of susceptibility and resilience. In Aims 2 and 3, I propose to test if
these projections are necessary or sufficient for susceptibility. Collectively, these experiments provide novel
insight into how VTA-NAc circuit activity contributes to the development of susceptibility in males and females.

## Key facts

- **NIH application ID:** 9855074
- **Project number:** 5K08MH109735-04
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Alexander Harris
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $196,957
- **Award type:** 5
- **Project period:** 2017-03-15 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9855074

## Citation

> US National Institutes of Health, RePORTER application 9855074, VTA-nucleus accumbens circuit dynamics underlying stress susceptibility (5K08MH109735-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9855074. Licensed CC0.

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