# Isolation of brain reward circuits using peptidergic systems

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $339,172

## Abstract

Project Summary
Dopamine neurons of the ventral tegmental area (VTA) provide essential modulatory signals to the forebrain
limbic system and cortex to facilitate learning and motivational processes. Disruptions in dopamine signaling
are broadly implicated in mental illness and likely contribute to a spectrum of behavioral dysfunction through
distinct cortico-limbic pathways. The heterogeneity of dopamine neurons in the VTA has long been
appreciated, but therapeutic strategies targeting the system are still based on a monolithic perspective. Recent
advances in mapping the input/output relationships of distinct dopamine pathways have attempted to resolve
the basic organization of the VTA, but have yielded little in the way of establishing how specialized
subdivisions might be organized. Unraveling the basic anatomical and functional organization of the VTA is
essential if precision therapeutics are to be achieved for treating specific behavioral dysfunctions. We
hypothesized that the dopamine system in the VTA can be organized based on peptidergic modulation to gate
information through specific output pathways. We have mapped the projections of dopamine neurons in the
VTA that express distinct neuropeptide receptors and discovered a remarkable specialization of these outputs.
Here we propose to establish the basic electrophysiological, anatomical, and behavioral function of these
pathways using novel Cre driver mouse lines in combination with advanced techniques in viral-based circuit
dissection. We will also establish novel methods for the genetic characterization of these subpopulations.
Successful completion of our proposed aims will provide novel insight into the basic organization of the VTA
dopamine system and establish a framework for cracking the dopamine code.

## Key facts

- **NIH application ID:** 10349478
- **Project number:** 5R01DA044315-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** LARRY S ZWEIFEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $339,172
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349478

## Citation

> US National Institutes of Health, RePORTER application 10349478, Isolation of brain reward circuits using peptidergic systems (5R01DA044315-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10349478. Licensed CC0.

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