# Context dependent modulations of dopamine signaling

> **NIH NIH R01** · HARVARD UNIVERSITY · 2020 · $422,500

## Abstract

Project Summary
Dopamine is thought to be a key regulator of learning from appetitive as well as aversive events. It has been
proposed that dopamine neurons signal value prediction error (VPE, often referred to as reward prediction
error), or the difference between the values of actual and predicted outcomes. Although accumulating evidence
supports this idea for reward, how dopamine neurons integrate information about aversive events remains
highly controversial. Some studies have shown that aversive stimuli inhibit dopamine neurons, while others
have suggested that aversive events activate at least some dopamine neurons. Others have argued that
dopamine neurons largely ignore aversive events. In order to resolve the above controversy, this project aims
to examine how dopamine neurons in the ventral tegmental area (VTA) convey information about aversive
events . Our main hypothesis is that dopamine neurons alter the way they respond to rewarding and aversive
stimuli depending on reward contexts. More specifically, we hypothesize that in low reward contexts, dopamine
neurons faithfully signal value prediction errors by combining the value of both reward and aversion. In high
reward contexts, we hypothesize that dopamine neurons acquire short-latency excitatory response to aversive
stimuli and decrease their inhibitory responses to aversive stimuli, thereby diminishing their ability to signal
value prediction errors. Aim 1 will test the specific hypothesis that dopamine neurons in VTA represent a
combined value for reward and aversion along a one-dimensional value axis in a low reward context. Aim 2 will
test the hypothesis that VTA dopamine neurons signal value prediction error in low but not high reward
contexts. Aim 3 will test the hypothesis that expectation of an aversive stimulus reduces aversive stimulus-
induced inhibition in a subtractive fashion in low reward contexts.
Malfunction of the midbrain dopamine system is associated with a variety of pathological conditions including
depression, anhedonia, apathy, schizophrenia, addiction, eating disorders and Parkinson's disease. In
particular, aberrant dopamine responses to salient events have been implicated in addiction, schizophrenia
and other mental disorders. This study will allow us to better understand situations in which dopamine neurons
are activated by aversive events, and will serve as a foundation to understand dopamine signaling in health
and disease.

## Key facts

- **NIH application ID:** 9874007
- **Project number:** 5R01MH110404-05
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Naoshige Uchida
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $422,500
- **Award type:** 5
- **Project period:** 2016-06-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874007

## Citation

> US National Institutes of Health, RePORTER application 9874007, Context dependent modulations of dopamine signaling (5R01MH110404-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9874007. Licensed CC0.

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