# Isolation of brain reward circuits using peptidergic systems

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $417,168

## Abstract

Project Summary
The neurotransmitter dopamine provides an important modulatory signal that facilitates a myriad
of brain functions. The heterogeneity of neurons in the VTA has long been appreciated, but
therapeutic strategies targeting the system are still based on a monolithic perspective. Recent
advances in genetics-based methods have provided new approaches to resolving the molecular
pathways that regulate the intrinsic properties of these cells that underlie their distinct functions
and likely confer unique pharmacological sensitivities. Using single nuclear RNA sequencing,
we defined unique genetic signatures within specific cell types that we hypothesize contributes
to their functionality. Specifically, we identified ion channel subunits that are differentially
expressed in dopamine subpopulations that confer unique electrophysiological properties to
essential voltage-gated potassium channels that we hypothesize contributes to differences in
the intrinsic excitability of these cells. We have also defined the unique circuit connectivity of
these cells. We will utilize a combination of genetic and pharmacological approaches to
understand how the regulation of ion channels and circuit connections contributes to the
specialization of these cell types. In addition to the genetic profile of specific populations, we
have identified a neuropeptide receptor that is expressed in subsets of the major projection
subpopulations. Activation of neurons that express this receptor is minimally sufficient to
promote reinforcement, but the function of this receptor and its intracellular signaling in this
context remain largely unknown. To address this, we will use a combination of pharmacology
and molecular genetics approaches to understand the intracellular signaling associated with this
receptor that confers its function within dopamine neurons. Collectively, the aims of this
proposal will provide important new insight into the molecular pharmacology of dopamine
subpopulations.

## Key facts

- **NIH application ID:** 10851023
- **Project number:** 5R01DA044315-07
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** LARRY S ZWEIFEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $417,168
- **Award type:** 5
- **Project period:** 2018-04-15 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10851023

## Citation

> US National Institutes of Health, RePORTER application 10851023, Isolation of brain reward circuits using peptidergic systems (5R01DA044315-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10851023. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*