# Neuron- and Circuit-Specific Mechanisms and Adaptations Regulating Motor Function in Parkinson Disease Models

> **NIH NIH R01** · J. DAVID GLADSTONE INSTITUTES · 2020 · $468,551

## Abstract

ABSTRACT
 Parkinson's disease (PD) is the second most common neurodegenerative disease (after Alzheimer's
disease), afflicting tens of millions worldwide. The characteristic disease symptoms arise from basal ganglia
dysfunction that occurs secondary to loss of dopamine neurons in the substantia nigra pars compacta.
Symptomatic treatment is focused either on replacing dopamine or disrupting aberrant activity through deep-
brain stimulation in the subthalamic nucleus or the primary basal ganglia output nucleus in the primate, internal
globus pallidus (GPi). This proposal is aimed at understanding the function and dysfunction of basal ganglia
circuitry in mice, at the output of the basal ganglia to motor thalamus. In Aim 1, we will develop strategies to
identify basal ganglia-recipient motor thalamus neurons in ventral anterior/ventral lateral thalamus (VA/VL),
and characterize their projection targets and cortical inputs in awake, behaving animals. In Aim 2, we will use
sophisticated in vivo strategies to record from posterior EP neurons and VA/VL neurons as animals move their
limbs during locomotion, a fixed repetitive behavior. We will perturb activity in this pathway using optogenetics
to determine the contribution of activity in these neurons to forelimb movements, and we will examine how
activity in this pathway is altered after loss of striatal dopamine. In Aim 3, we will perform similar experiments in
mice performing a lever-pulling task, a flexible forelimb movement. We will examine both cued and uncued
versions of this task to distinguish activity generated internally vs. externally. Finally, we will examine how loss
of striatal dopamine impacts EP and VA/VL activity during flexible forelimb movements. Our overarching goal is
to understand how loss of striatal dopamine in PD leads to disruptions in basal ganglia circuit function and
motor deficits, in order to develop novel therapeutic strategies for treating PD motor symptoms.

## Key facts

- **NIH application ID:** 9971314
- **Project number:** 2R01NS064984-11A1
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** ANATOL KREITZER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $468,551
- **Award type:** 2
- **Project period:** 2009-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971314

## Citation

> US National Institutes of Health, RePORTER application 9971314, Neuron- and Circuit-Specific Mechanisms and Adaptations Regulating Motor Function in Parkinson Disease Models (2R01NS064984-11A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971314. Licensed CC0.

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