# Dissecting the dual role of dopamine in context-dependent and learned behaviors

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $389,850

## Abstract

Project Summary
Dopamine plays a central role in motivation and reinforcement learning, allowing animals to take advantage of
their current circumstances to optimize both present and future behavior. Yet reconciling the diverse roles of
dopamine has remained a challenge, in part due to the difficulty of understanding how a single neuromodulator
can convey different signals to its cellular targets in distinct behavioral contexts. One prominent model is that
different patterns of dopamine release engage distinct molecular pathways in downstream circuits, such that
tonic fluctuations in dopamine regulate motivation while phasic bursts of dopamine convey reward prediction
errors for learning. However, recent work has suggested that phasic firing patterns can both instruct learning and
convey motivational signals that promote movement, challenging this simple dichotomy. Here we propose to use
the Drosophila mushroom body as a powerful model to dissect dopamine’s diverse roles in modulating behavior.
Recent work from our lab has shown that the same mushroom body dopaminergic neurons (DANs) responsive
to rewards that instruct learning also reflect an animal’s purposive actions, underscoring how the dual
representation of reward and locomotion is a conserved feature of dopaminergic systems from flies to mammals.
Taking advantage of the mushroom body’s simple circuit architecture and unparalleled genetic toolkit, we will
build on these observations to reveal how reward and locomotor signals are directly translated to different
patterns of dopamine release and engage distinct dopamine receptor signaling cascades to shape circuit
processing and behavior. In Aim 1, we will perform multicolor functional imaging as animals navigate in a virtual
olfactory environment and reveal how tonic and phasic patterns of DAN activity are propagated to their post-
synaptic targets. In Aim 2 we will use a suite of optical sensors to measure dopamine release and dopamine
receptor signaling to understand how the same neuromodulator engages different sub-cellular cascades in
different behavioral contexts. In Aim 3 we will test how animals use tonic DAN activity to regulate their ongoing
behavior. Dysfunction in dopaminergic signaling is at the core of a wide array of neuropsychiatric conditions,
from the severe motor deficits of Parkinsonian patients to motivational disorders like depression and drug
addiction. By applying a multidisciplinary approach to interrogate the relatively simple dopaminergic circuitry of
the fly, we hope to provide an integrative understanding of dopamine’s diverse actions with important implications
to understanding neuromodulation in both healthy and diseased states.

## Key facts

- **NIH application ID:** 9975247
- **Project number:** 5R01NS113103-02
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Vanessa Ruta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,850
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975247

## Citation

> US National Institutes of Health, RePORTER application 9975247, Dissecting the dual role of dopamine in context-dependent and learned behaviors (5R01NS113103-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975247. Licensed CC0.

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