# The diversity of dopamine neurons: from connectivity and activity to functions.

> **NIH NIH R01** · HARVARD UNIVERSITY · 2020 · $536,702

## Abstract

Project Summary
Dopamine neurons (DNs) are key regulators of motivated behaviors, and defects in dopamine
signaling may underlie some psychiatric disorders including addiction, depression, and schizophrenia,
as well as neurological disorders such as Parkinson's. Much of the work in this area has been based
on the dogma that DNs encode reward prediction errors (RPE) and that they do so in a uniform
manner. However, work from several groups, including ours, indicates that DNs projecting to different
targets exhibit distinct properties and serve distinct functions. In this proposal, we aim to link the
diversity of DNs defined by their connectivity and activity with their functions.
One recent example, drawn from our work, is that DNs projecting to the posterior `tail' of the striatum
(TS) differ in many ways from DNs projecting to the ventral striatum (VS) and other regions. VS-
projecting DNs, which signal `canonical' RPEs, are activated by reward and inhibited by negative
events. By contrast, TS-projecting DNs are activated by novel stimuli and a subset of negative
events.
Here, based on our initial results, we will compare VS- and TS-projecting DNs with regard to their (1)
activity, (2) function during behaviors, and (3) mechanism underlying the generation of the activities.
We will test the main hypothesis that TS-projecting DNs integrate a unique set of inputs, signal threat
prediction errors, and positively reinforces threat predictions or avoidance behaviors. Specific Aim 1
will characterize the activity of projection-specific DNs during behavior. Specific Aim 2 will
demonstrate the causal link between the function and the activity patterns of projection-specific DNs.
Specific Aim 3 will aim to understanding neural circuit mechanisms that generate distinct response
patterns of DNs in a projection-specific manner. If our main hypothesis holds true, the results will
demonstrate that dopamine in VS and TS operates in a similar manner at the algorithmic level: in
both systems, an increase in dopamine results in facilitation of certain behaviors (approach or
avoidance) or stimulus-based predictions (of outcome value or a threat). The methods and results of
the proposed study will pave the way for looking at other DN populations in the future. This will further
the goal of elucidating a unifying theory regarding the computational algorithm by which multiple DN
populations function. We expect these results to provide insights into dopaminergic defects and even
dopamine-directed therapeutic interventions in brain disorders.

## Key facts

- **NIH application ID:** 9999693
- **Project number:** 5R01NS108740-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Naoshige Uchida
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $536,702
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999693

## Citation

> US National Institutes of Health, RePORTER application 9999693, The diversity of dopamine neurons: from connectivity and activity to functions. (5R01NS108740-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999693. Licensed CC0.

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