# Dopamine modulation of synaptic plasticity and integration in the striatum

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $473,915

## Abstract

Project Summary:
 Learning and executing motor skills are crucial functions of the brain and involve the coordinated activity of
the motor cortex and basal ganglia. Notably, the connections between the primary motor cortex (M1) and the
dorsolateral striatum (DLS), a major target of M1 output neurons, are crucially involved in motor learning. Loss-
of-function studies, such as DLS lesions or silencing spiny projection neurons (SPNs) impairs learned motor
behaviors, and blocking SPN plasticity by deleting NMDA receptors on SPNs prevents mice from learning new
motor skills. In addition, in movement disorders, such as Parkinson’s disease and L-DOPA-induced dyskinesia,
disruption of ensemble activity of neurons in the DLS or M1 may mediate behavioral deficits. Yet, direct
evidence of plasticity and dynamics of corticostriatal synapses during motor learning is surprisingly lacking.
One reason for this gap is the widespread and convergent innervation of corticostriatal projections which has
made it challenging to assess the function and plasticity of this circuit over the course of motor learning. How
corticostriatal synaptic plasticity contributes to motor learning and the formation of motor memory in vivo
remains unclear. Motor learning leads to adaptation of neuronal activity patterns in M1 as well as in DLS and
their activity becomes more closely associated with learned movements. An intriguing interpretation of these
adaptations in neuronal activity is that such behavior-related neurons may represent the neural correlate of
motor memory, forming a motor memory engram. Here, we hypothesize that motor learning induces synaptic
plasticity in the corticostriatal motor engram neurons, which is crucial for the formation and consolidation of
motor memory. In this proposal, using approaches combining such genetic tools to label and manipulate motor
engram neurons with electrophysiology, ex vivo and in vivo 2-photon imaging, and single-cell RNA-
sequencing, we aim to investigate how corticostriatal circuit adapts during motor learning at molecular, cellular,
and circuit levels. The major goals are: 1: To investigate cortical and striatal excitatory synaptic plasticity of
motor engram neurons. 2: To examine how motor learning affects the structure and function of corticostriatal
projections. 3. To determine the molecular mechanism underlying corticostriatal synaptic plasticity induced by
motor learning. Success in the proposed experiments will provide an in-depth, mechanistic understanding of
synaptic plasticity and integration in the corticostriatal circuits. Given the fundamental role of synaptic plasticity
in the learning and execution of motor skills and maladaptive cortical and striatal synaptic plasticity seen in
movement disorders, our findings may further contribute to future strategies to more effectively treat these
diseases, such as Parkinson’s disease.

## Key facts

- **NIH application ID:** 10862634
- **Project number:** 5R01NS091144-08
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jun Ding
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $473,915
- **Award type:** 5
- **Project period:** 2015-04-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862634

## Citation

> US National Institutes of Health, RePORTER application 10862634, Dopamine modulation of synaptic plasticity and integration in the striatum (5R01NS091144-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10862634. Licensed CC0.

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