# Dopaminergic regulation of spatial learning

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2022 · $423,750

## Abstract

Summary
In neural networks that store information in their connection weights, there is a tradeoff between sensitivity
and stability. Connections must be plastic to incorporate new information, but if they are too plastic, stored
information can be corrupted. Therefore, it would be useful if learning rates in the brain were regulated by a
“when-to-learn” signal that varies with the current availability of new information. In reward learning,
dopamine is known to serve this function, by rapidly upregulate synaptic plasticity in response to reward
prediction errors. The overarching hypothesis of this proposal is that dopamine also provides a when-to-learn
signal for spatial learning. During spatial learning, new information is generally available when an organism is
moving through space. Thus, we hypothesize that spatial learning is modulated by dopamine release that is
specifically linked to active movements. This idea is attractive because it can provide an explanation for why so
many dopamine neurons are time-locked to movements. This proposal outlines three projects, all focusing on
spatial learning in the central complex, the primary center for spatial navigation in the Drosophila brain. In
each project, there is anatomical evidence from the Drosophila connectome that implies a role for dopamine
neurons. Moreover, in each project, there is already evidence that the dopamine neurons in question are active
when the fly is locomoting. This motivates our hypothesis that dopamine links movement to spatial learning.
Although these projects are linked conceptually, they each focus on a distinct dopamine cell type, and a distinct
form of spatial learning. First, we will determine how dopamine modulates learning about spatial position cues
in the head direction system. Second, we will investigate the hypothesis that dopamine modulates learning
about rotational velocity cues in the head direction system. Third, we will investigate the hypothesis that a
feedback circuit integrates information over time to discount the influence of environmental wind shifts on
head direction neurons. In all three projects, we use connectome analyses and computational modeling to
generate testable predictions about specific networks in the brain. Then, we test these predictions using in vivo
calcium imaging and/or electrophysiology as flies navigate in virtual reality environments. Our results should
shed light on the fundamental mechanisms underlying navigation behaviors in all complex species, including
ring attractor networks, Hebbian learning rules, and feedback loops. Broadly speaking, we think that dopamine
provides a control knob for modulating these mechanisms up or down. As such, we see dopaminergic neurons
as an entry point for an integrative understanding of network dynamics during complex cognitive processes.

## Key facts

- **NIH application ID:** 10561863
- **Project number:** 1R01NS129647-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Rachel Wilson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,750
- **Award type:** 1
- **Project period:** 2022-09-22 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10561863

## Citation

> US National Institutes of Health, RePORTER application 10561863, Dopaminergic regulation of spatial learning (1R01NS129647-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10561863. Licensed CC0.

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