# Circuit-specific mechanisms of reward and aversion in ventral tegmental area dopamine neurons

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2023 · $556,393

## Abstract

ABSTRACT
Cue-driven behaviors are actions motivated by salient environmental stimuli. Maladaptive changes in cue-
driven behaviors are fundamental to several neuropsychiatric disorders, including substance use disorder.
Ventral tegmental area (VTA) dopamine (DA) neurons have often been assumed to homogeneously encode
reward prediction errors. However, even within the nucleus accumbens (NAc), which is the major
projection target of VTA DA neurons, DA release has been implicated in several behavioral functions,
including reward, aversion, motivation, and incentive salience. This discrepancy might be, at least in part,
due to the different methodologies used to record DA cell body activity versus DA release at the axon
terminal level. Additionally, recent investigations suggest that VTA DA neurons might differentially
contribute to reward and aversion dependent on their projection target and mediolateral position within the
VTA. Here, we propose to further detail and define, in a circuit- and cell-type specific manner, the
functional heterogeneity of the mesoaccumbal DA system. We will employ a three-pronged approach that
leverages pharmacological manipulations, fiber photometry-based recordings of DA cell body activity and
DA release, as well as in vivo electrophysiological recordings of DA neurons using Neuropixels and
optogenetics. Our investigations will that takes the precise neuroanatomical position of DA neurons within
the VTA and their corresponding NAc projection target into consideration. Experiments will be performed
in head fixed mice during pharmacological manipulation or during reward seeking behavior as well as in
freely behaving mice performing a two-armed bandit task. This will allow us to test whether DA dynamics
mediated by different mechanisms in different locations (i.e., at the level of cell bodies versus terminals)
underlie distinct behavioral functions. The primary goals are to (1) investigate how different doses of
nicotine modulate DA release in distinct NAc subregions. Additionally, we will provide a systematic
understanding of how nicotinic acetylcholine receptor function contributes to nicotine-induced DA release
in different NAc subregions. (2) We will study how DA cell body activity and DA release in separate
mesoaccumbal subcircuits contributes to reward learning and motivated behavior. (3) We will establish an
in vivo electrophysiological approach that utilizes Neuropixels and optogenetics to record VTA DA neurons
in a circuit- and cell-type specific manner in head fixed mice performing a reward seeking task. Together,
we anticipate that these experiments will provide further evidence for our hypothesis that VTA DA neurons
make specific contributions to reward learning and motivation in a projection-defined manner. Delineating
the precise functions of separate mesoaccumbal DA subcircuits for reward learning and motivated behavior
is a significant step in improving our understanding of their diverse roles in health an...

## Key facts

- **NIH application ID:** 10585085
- **Project number:** 2R01DA042889-06A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Stephan Lammel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $556,393
- **Award type:** 2
- **Project period:** 2017-06-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10585085

## Citation

> US National Institutes of Health, RePORTER application 10585085, Circuit-specific mechanisms of reward and aversion in ventral tegmental area dopamine neurons (2R01DA042889-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10585085. Licensed CC0.

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