# The role of VTA neurotransmitter co-release in health and disease

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $66,390

## Abstract

PROJECT SUMMARY
 Elucidating the neural circuit mechanisms underlying both homeostatic and uncontrolled motivation are
crucial for developing better therapeutic treatments for neuropsychiatric disorders like depression or bipolar
disorder.
 As part of mesolimbic brain reward circuitry, the ventral tegmental area (VTA) is generally reduced to its
dopamine projection neurons. However, VTA also contains neurons that co-release inhibitory GABA and
excitatory glutamate that are capable of powerfully modulating motivation. However, the functional role of this
GABA/glutamate co-release in health and disease is not well understood. Why would these neurons
simultaneously send both a `stop' and `go' signal?
 This set of proposed experiments will systematically test the hypothesis that VTA GABA/glutamate co-
release serves as a mechanism to normalize postsynaptic activity in a homeostatic manner. Using
optogenetics to drive VTA GABA/glutamate co-release in downstream structures that regulate mood and
motivation, I will use chemogenetic approaches and chronic behavioral manipulations that alter postsynaptic
activity, and then test the physiological and behavioral effect of optogenetically driving VTA GABA/glutamate
co-release. These experiments will reveal basic mechanisms of neurotransmitter co-release and uncover their
role within mesolimbic circuitry in modulating the switch between reward and aversion. The proposed
experiments will also provide the investigator with extensive training in cell-attached and whole-cell patch
clamp electrophysiology, and mouse genetics.
 Showing a brain mechanism capable of normalizing activity and in turn motivation can provide a novel
target for treating neuropsychiatric diseases, as well as elucidate the mysterious role of neurotransmitter co-
release beyond neuropsychiatric disease.

## Key facts

- **NIH application ID:** 10078844
- **Project number:** 5F32MH122192-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Shelley May Warlow
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10078844

## Citation

> US National Institutes of Health, RePORTER application 10078844, The role of VTA neurotransmitter co-release in health and disease (5F32MH122192-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10078844. Licensed CC0.

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