# Pathophysiology of the Pedunculopontine Nucleus in Parkinson's Disease

> **NIH NIH R01** · EMORY UNIVERSITY · 2021 · $486,882

## Abstract

SUMMARY
According to current models, the involvement of the basal ganglia in motor and non-motor functions is explained
in the context of information processing in segregated basal ganglia-thalamocortical loops. These models predict
that striatal dopamine loss in Parkinson’s disease (PD) eventually leads to abnormal processing in the “motor”
thalamocortical network, and the antiparkinsonian effects of deep brain stimulation (DBS) of the sensorimotor
internal globus pallidus (GPi) is explained as a release of movement-related thalamic neurons from overactive
inhibitory GPi inputs. However, recent evidence suggests that descending basal ganglia output, specifically the
massive projection of GPi to the pedunculopontine nucleus (PPN), may also be relevant for normal behavior and
parkinsonism. Thus, manipulations of the PPN influence limb movements and postural adjustments, PPN
activation has antiparkinsonian effects in monkeys, and DBS of the PPN ameliorates gait disturbances in some
PD patients. The PPN is a highly heterogeneous brain region that gives rise to widespread ascending and
descending projections. Our lack of knowledge of the anatomical targets of GPi projections to the PPN, and the
effects of activation of the GPi-PPN pathway on PPN activity limits our understanding of the normal role of the
GPi-PPN interaction and its role in the pathophysiology of PD, particularly in primates. The proposed studies aim
therefore to examine the functional connectivity between the GPi and the PPN (aims 1 and 2), determine whether
the anatomy and physiology of these networks are altered in the parkinsonian state (aims 2 and 3), and how
GPi-DBS alters firing rates and patterns of GPi-receiving PPN neurons, as well as local field potential activity in
the PPN (aim 3). These studies will be done in normal and MPTP-treated parkinsonian monkeys, using a
combination of state-of-the-art optogenetic, anatomical and electron microscopy procedures. The knowledge
gained from these studies is needed to develop or refine antiparkinsonian therapies that target the PPN or its
projections for treatment of PD or other basal ganglia disorders.

## Key facts

- **NIH application ID:** 10213844
- **Project number:** 5R01NS098441-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Yoland Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $486,882
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213844

## Citation

> US National Institutes of Health, RePORTER application 10213844, Pathophysiology of the Pedunculopontine Nucleus in Parkinson's Disease (5R01NS098441-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213844. Licensed CC0.

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