# Determining the function of TRPC6 channels in a subpopulation of VTA dopamine neurons

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2024 · $45,355

## Abstract

Project Summary/Abstract:
Midbrain dopamine (DA)-producing neurons of the ventral tegmental area (VTA) play a critical role in
modulating reward-seeking behavior. VTA-DA neurons are functionally and genetically heterogeneous, and
genetic markers for neuropeptides and neuropeptide receptors can be used to isolate VTA subpopulations.
Though distinct neuropeptidergic pathways have been shown to potently modulate DA neurons, the
intracellular signaling pathways that act downstream of neuropeptide receptors are unknown. VTA-DA neurons
that express the Gq-protein coupled receptor, tachykinin receptor 3 (Tacr3), are a minimally sufficient
subpopulation of DA neurons that promote reward reinforcement behavior. Tacr3 activation has recently been
shown to be dependent on transient receptor potential canonical (TRPC) channel signaling in the
hypothalamus. TRPC type 6 (TRPC6) channels are enriched in DA neurons and are activated by stimulation of
Gq-coupled receptor signaling. Therefore, I hypothesize that TRPC6 is likely the main type of TRPC channel in
VTA-DA neurons that acts downstream of Tacr3 activation. To establish the role of TRPC6 in regulating the
physiology and function of VTA-Tacr3 neurons, I propose to selectively mutate the Trpc6 gene to generate a
loss of function in a cell-type specific manner within the VTA of adult mice using an advanced CRISPR/Cas9
genetic technology. I will perform ex vivo slice electrophysiology and slice calcium imaging (Aim 1), as well as
in vivo recordings of calcium dynamics during a probabilistic discounting paradigm and progressive ratio
motivational task (Aim 2). Determining the function of TRPC6 in VTA-Tacr3 neurons will provide important
insights into the therapeutic potential of this understudied ion channel in the central nervous system.

## Key facts

- **NIH application ID:** 10974016
- **Project number:** 5F31DA058381-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Mollie Xiaoqi Bernstein
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,355
- **Award type:** 5
- **Project period:** 2023-09-16 → 2025-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974016

## Citation

> US National Institutes of Health, RePORTER application 10974016, Determining the function of TRPC6 channels in a subpopulation of VTA dopamine neurons (5F31DA058381-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10974016. Licensed CC0.

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