# Orbitofrontal Cortex - Ventral Tegmental Area Projection Neurons: Mapping Function to an Anatomically and Molecularly Distinct Neural Subpopulation

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2022 · $51,753

## Abstract

PROJECT SUMMARY/ABSTRACT
Poor decision-making is both a cause and a consequence of addiction. Though dysfunction of the orbitofrontal
cortex (OFC) is thought to underlie decision-making deficits in addicts, a circuit-based mechanism has not been
identified due to overwhelming functional heterogeneity. Preliminary retrograde labelling experiments suggest
that individual OFC projection neurons selectively target subcortical structures, but it is unknown if this
anatomical separation mirrors a functional division-of-labor and a fundamental subcortical sorting principle.
Integrating state-of-the-art techniques from functional genetics and electrophysiology, the objective of this
proposal is to directly map a decision-making variable to a distinct cell-type in the OFC. The proposed aims will
test the central hypothesis that that there is a division-of-labor between different OFC output neurons and more
specifically, that OFC-to-VTA projection neurons represent a distinct output tract that selectively routes choice
value. In Aim 1, I will determine the target selectivity of OFC-to-VTA projection neurons at a single neuron
resolution. In Aim 2, I will determine if OFC-VTA projection neurons represent a genetically-distinct cell-type. In
Aim 3, I will provide cell-type specific recordings in rats performing a rich, perceptual decision-making task and
determine the role of OFC-VTA projection neurons in supporting choice behavior. These studies contribute to a
mechanistic understanding of how decisions are computed and potentially, reveal an overarching, fundamental
principle that governs cortical-subcortical information distribution in the OFC. The proposed studies lay the
foundation for the identification of cell-type specific dysfunction in addiction and in future, the development of
more effective, circuit-based therapies. Ultimately, this proposal serves to prepare me for a career as an
independent physician-scientist. I will obtain a unique and multi-disciplinary skill-set that, in the future, will enable
me to better bridge the gap between experimental neuroscience and clinical practice.

## Key facts

- **NIH application ID:** 10405473
- **Project number:** 5F30MH120935-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Suelynn Ren
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,753
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405473

## Citation

> US National Institutes of Health, RePORTER application 10405473, Orbitofrontal Cortex - Ventral Tegmental Area Projection Neurons: Mapping Function to an Anatomically and Molecularly Distinct Neural Subpopulation (5F30MH120935-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10405473. Licensed CC0.

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