# Elucidating the Role of Neural Activity in Midbrain Dopamine Neuron Degeneration

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $43,464

## Abstract

PROJECT SUMMARY/ABSTRACT
Parkinson’s Disease (PD) is a debilitating neurodegenerative disease characterized by the progressive loss of
substantia nigra pars compacta (SNc) dopamine neurons. The reasons for their selective vulnerability and the
mechanisms that drive their degeneration remain unclear. There is mounting evidence that the activity of
energetically-burdened SNc neurons is altered in PD, however the role of neural activity in the susceptibility of
dopamine neurons is poorly understood. Additionally, while dopamine is known to be toxic to neurons that do
not have a means of sequestering or metabolizing it, the role of dopamine itself in the degeneration of dopamine
neurons in PD is not known. To investigate the role of activity in dopamine neuron selective vulnerability, we
have developed novel mouse models in which we can chronically manipulate midbrain dopamine neuron activity
using chemogenetics. With these models, we propose to determine how chronically manipulating activity and
dopamine metabolism within dopamine neurons impacts their susceptibility to degeneration. These experiments
will be the first to directly interrogate the role of neural activity in degeneration in a chronic, minimally-invasive
manner. Furthermore, they will provide insight for future therapeutic strategies to protect dopamine neurons from
degeneration in PD.

## Key facts

- **NIH application ID:** 10901737
- **Project number:** 1F31NS137765-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Katerina Rademacher
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,464
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901737

## Citation

> US National Institutes of Health, RePORTER application 10901737, Elucidating the Role of Neural Activity in Midbrain Dopamine Neuron Degeneration (1F31NS137765-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10901737. Licensed CC0.

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