# Mapping neurochemical activity of the basal ganglia in pathological behaviors

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $249,000

## Abstract

Project Summary Abstract
Improved strategies are needed to treat movement disorders, such as Parkinson’s disease (PD), which
debilitates more than 10 million people worldwide. PD, in addition to many other neurological disorders,
centrally involve dopamine neurochemical dysregulation. Current treatment for PD involves replenishing
dopamine through systemic L-Dopa administration. These treatments, however, display limited efficacy and
can have detrimental side-effects. The neurochemical pathophysiology is not well understood in these
disorders. This limited understanding hinders development of better therapies. It has been shown that
dopamine is dysregulated in a spatially heterogeneous pattern in PD, and the site-specific dopamine
operations have specific roles in the generation of pathology. The goal of this proposal is to dynamically map
the dopamine signals that mediate specific PD-implicated motor and mood behaviors in nonhuman primates.
New arrayed neurochemical probes have been developed to permit dopamine mapping in rodents. We have
recently confirmed our ability to measure multi-site dopamine neurochemicals, chronically, in the nonhuman
primate, using fast scan cyclic voltammetry (FSCV) electrochemical recording to measure dopamine at
subsecond timescales. Aim 1 of this proposal is to chart the spatially-distributed dopamine signaling in the
striatum of rats with receptor-selective pharmacological modulation and post-hoc chemically labeled co-
localization of measured sites. An expected outcome of this aim is a classification of dopamine dynamics in
terms of regional and structural striatal domains. Aim 2 of this proposal is to measure dopamine across striatal
sites in the task performing nonhuman primate to correlate site-specific dopamine with metrics of behaviors
implicated in PD. The results from this aim will elucidate how dopamine signals mediate key movement and
mood behavioral processes that are degraded in PD, and how these signals are distributed across the
striatum. A functional map of dopamine could help inform better treatment strategies based on current
symptomatic diagnostic criteria. Aim 3 involves measuring and mapping the interaction between two hallmarks
of PD, dopamine and beta-band local field potential (LFP), using acute and chronic models of PD in rodents
and nonhuman primates. The concurrent dopamine and LFP measurements will provide more quantitative
markers of pathology and enable improved strategies for diagnosing and treating PD. The proposed work for
Aims 1 and 2 will be performed during the K99 mentored stage, during which I will continue my training in
primate neurophysiology, surgery, and immunohistochemistry. These trainings will be pivotal in transitioning to
independence in the R00 independent investigator stage, during which Aim 3 will be executed.

## Key facts

- **NIH application ID:** 10489437
- **Project number:** 5R00NS107639-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Helen N Schwerdt
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489437

## Citation

> US National Institutes of Health, RePORTER application 10489437, Mapping neurochemical activity of the basal ganglia in pathological behaviors (5R00NS107639-04). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10489437. Licensed CC0.

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