# VTA dopamine neurons and cognitive symptoms of Parkinson’s disease

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $432,841

## Abstract

Abstract
Cognitive symptoms of Parkinson’s disease (PD) can affect up to 80% of PD patients and lead to
enormous societal cost. These symptoms involve impaired executive functions such as working memory,
attention, behavioral flexibility, and timing, and can progress to psychosis, hallucinations, and dementia.
There are few therapies that improve cognitive function in PD. Thus, there is a critical need to better
understand the fundamental mechanisms of cognitive dysfunction that occurs in PD. Our long-term goal
is to elucidate the mechanisms by which cognitive dysfunction occurs in PD patients in order to develop
new targeted treatments.
PD involves death of midbrain dopaminergic neurons in ventral tegmental area (VTA). These neurons
send mesocortical projections to key cognitive cortical areas such as the prefrontal cortex. It is unknown
how VTA dopamine neurons are involved in cognitive processes that malfunction in human PD patients.
Our goal in this proposal is to harness cell-type specific rodent models to characterize VTA dopamine
neuronal function in cognitive processes relevant to PD. Our preliminary data demonstrates interval-
timing variability correlates with PD-related cognitive dysfunction. Our rodent research demonstrates that
VTA dopamine is necessary for interval timing, prefrontal timing-related modulations and prefrontal 4 Hz
rhythms. Here, we will combine optogenetics, fiber photometry, and neuronal ensemble recordings in
transgenic mice to interrogate VTA dopamine projections with cell-type-specificity and millisecond
resolution. We will test the overall hypothesis that VTA dopamine neurons engage cognitive processing
in the prefrontal cortex. In Aim 1 we will determine how silencing VTA dopamine neurons impacts
cognitive processing. In Aim 2 we will define how VTA dopamine neuron dynamics predict cognitive
processing. In Aim 3 we will determine how stimulating VTA dopamine neurons impacts cognitive
processing.
This proposal is broadly significant in determining when and how VTA dopamine engages prefrontal
cognitive processing. Although this is a basic-science proposal focused on VTA dopamine neurons, our
results will guide new therapies for human PD. This work could contribute to biomarkers for PD and for
other Alzheimer’s disease and related dementias (ADRDs) such as dementia with Lewy bodies (DLB).

## Key facts

- **NIH application ID:** 10176823
- **Project number:** 1R01NS120987-01
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Nandakumar Narayanan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,841
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176823

## Citation

> US National Institutes of Health, RePORTER application 10176823, VTA dopamine neurons and cognitive symptoms of Parkinson’s disease (1R01NS120987-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176823. Licensed CC0.

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