# Ion channel mechanisms of striatal dopaminergic motor stimulation

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2020 · $332,500

## Abstract

Loss of dopamine in the striatum quickly leads to akinesia and is a key pathology of Parkinson's disease. L-
dopa, via dopamine, strongly stimulates motor activity in Parkinson's disease patients and dopamine-
depleted animals. However, the ion channel and neurophysiological mechanisms underlying dopamine's
profound motor function remain unknown; this knowledge gap is an obstacle to improving the treatment of
this disease.
 Using suitable mouse models with color-labeled striatonigral neurons and striatopallidal neurons and
consistent dopamine denervation, and combining patch clamp recording in a well controlled brain slice
preparation and tetrode spike recording in freely moving mice, this project will test our hypothesis that
dopamine D1 receptor activation upregulates the subthreshold-activating and persistent sodium current in
striatonigral neurons and thus, increases the motor-promoting spike output from these neurons, contributing
to dopamine's motor stimulation; these effects are enhanced when the D1 receptors are supersensitive after
dopamine denervation such as in Parkinson's disease. Simultaneously, dopamine D2 receptor activation
downregulates the persistent sodium current in striatopallidal neurons and hence decreases the motor-
inhibiting spike output from these neurons, further contributing to dopamine's motor stimulation; these
effects are also enhanced when the D2 receptors are supersensitive following dopamine denervation.
Preliminary results support our hypothesis.
 In summary, this project will use integrative approaches to define fundamental ion channel and
neurophysiological mechanisms by which dopamine D1 receptor activation excites striatonigral neurons and
dopamine D2 receptor activation inhibits striatopallidal neurons. Results of this research will provide critical
insights into the long-standing question of how dopamine stimulates motor activity and will also lay a
scientific foundation for improving the treatment for the motor symptoms of Parkinson's disease.

## Key facts

- **NIH application ID:** 9920785
- **Project number:** 5R01NS097671-05
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** FU-MING ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,500
- **Award type:** 5
- **Project period:** 2016-09-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920785

## Citation

> US National Institutes of Health, RePORTER application 9920785, Ion channel mechanisms of striatal dopaminergic motor stimulation (5R01NS097671-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9920785. Licensed CC0.

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