# Dopamine, Synaptic Plasticity and Striatal Ensemble Dynamics Underlying Motor Learning

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $453,272

## Abstract

PROJECT SUMMARY/ABSTRACT
Dopamine signaling in the striatum is critical for movement, yet the mechanistic basis for its permissive role in
motor actions is incompletely understood. The longstanding view is that dopamine promotes movement by
differentially modulating the striatum’s principal neurons, the D1 and D2 dopamine receptor expressing spiny
projection neurons (SPNs). Specifically, striatal dopamine is thought to increase D1- and decrease D2-SPN
excitability. This view has strong support from 1) ex vivo measurements of dopamine’s effects on D1- and D2-
SPN excitability and the in vivo observations that 2) ablating dopamine neurons decreases D1- and increases
D2-SPN activity and 3) the selective activation of D1- or D2-SPNs respectively promotes or suppresses
movement. However, several recent findings from in vivo recordings of D1- and D2-SPN activity do not support
a simple “go/no-go” model for D1- and D2-SPN function in movement. Specifically, in vivo recordings have shown
that D1- and D2-SPNs co-activate in spatially overlapped clusters, both increase their activity at higher running
speeds, and both decrease their activity at motion offset. Therefore, it remains unclear precisely which aspects
of D1- and D2 activity (e.g., levels, timing, or spatial coordination) are modulated by dopamine signaling and how
this promotes movement. To address these questions, we have developed three, multiphoton imaging
approaches to simultaneously record 1) D1- and D2-SPN activity, 2) dopamine axon activity and D1- or D2-SPN
activity, and 3) immediate early gene expression tagging and D1- or D2-SPN activity in vivo. We will use these
tools to image neural activity during training in a dopamine-dependent, conditioned-avoidance motor learning
task. Our preliminary data indicate that dopamine is released during learned movement in this task, and that D1-
and D2-SPNs encode these movements with different levels, timing, and spatial coordination. We hypothesize
that these changes are necessary for motor learning and result from dopamine’s gradual and differential effects
on the strength of excitatory synaptic connections in specific subsets of D1- and D2-SPNs. We will test this
hypothesis by integrating the results from our in vivo imaging experiments with ex vivo measurements of synaptic
strength in D1- and D2-SPNs. Overall, our experiments have the potential to resolve a central conflict in our
understanding of dopamine’s role in motor control and how this process goes awry in neurological and psychiatric
disease.

## Key facts

- **NIH application ID:** 10276959
- **Project number:** 1R01NS122840-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Jones G Parker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $453,272
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276959

## Citation

> US National Institutes of Health, RePORTER application 10276959, Dopamine, Synaptic Plasticity and Striatal Ensemble Dynamics Underlying Motor Learning (1R01NS122840-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276959. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*