# The role of the centromedian and pedunculopontine nuclei in motor function during naïve, parkinsonian and DBS conditions

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2020 · $43,760

## Abstract

ABSTRACT
 Parkinson's Disease (PD) is the second most common neurodegenerative disease and affects up to
3% of the population in industrialized countries. Patients in the advanced stages of the disease can partake in
different therapies, including deep brain stimulation (DBS). This particular therapy can ameliorate symptoms of
tremor, bradykinesia, akinesia and rigidity of the limbs, however, there is an unmet need to increase the
effectiveness of this therapy on gait dysfunction, a symptom of the disease that can drastically reduce the
quality-of-life of patients. Recently, there has been interest in novel targets for deep brain stimulation in order
to address this deficit. Two brain areas, the mesencephalic locomotor region (MLR) and the centromedian-
parafascicular nucleus of the thalamus (CM-Pf) have been identified as involved in initiation, halting or
modulating locomotion and selecting new motor actions in the context of changing sensory environments,
respectively, and clinical trials have been conducted with mixed results. While the roles of these nuclei in motor
function have been illustrated in the literature, it is unknown how the signaling of these nuclei change from a
naïve to parkinsonian state and how DBS in the basal ganglia further perturbs their firing. The overall goal of
this project is to understand the firing changes in these structures after parkinsonian onset in a non-
human primate MPTP-model of PD and how DBS targeting traditional DBS targets, such as the
subthalamic nucleus and globus pallidus internus, exacerbates or facilitates their signaling. Aim 1 of
this proposal will be to record from the MLR during naturalistic gait and characterize firing changes and
behavioral changes seen with parkinsonism and different DBS stimulation. Aim 2 will include the same
methods, but in CM, and furthermore, it will include studying the circuit dynamics of MLR-CM through
simultaneous recording in these structures. Preliminary data has validated the behavioral paradigm and
changes in gait variables can be seen after DBS application. The results of this proposal will elucidate the
mechanisms of the MLR and CM in normal gait function and the electrophysiological changes that
occur after parkinsonism and DBS onset. This will provide much-needed information in these
structures that cannot be gleaned from PD patients in the clinic and, furthermore, it will provide clues
on how to improve current DBS therapy.

## Key facts

- **NIH application ID:** 9977294
- **Project number:** 5F31NS108625-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Alexandra Marie Doyle
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $43,760
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-09-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977294

## Citation

> US National Institutes of Health, RePORTER application 9977294, The role of the centromedian and pedunculopontine nuclei in motor function during naïve, parkinsonian and DBS conditions (5F31NS108625-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977294. Licensed CC0.

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