Team Edwards

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Circuitry and Brain-Body Interactions | 2021

Dual Role of Neural Activity in Parkinson’s Disease

Study Rationale: Previous work has shown how the loss of dopamine neurons affects brain activity. In this program, Team Edwards will determine how brain activity influences the neurodegeneration that causes Parkinson’s disease (PD). To understand the onset of disease, the team will identify the earliest changes in brain activity and use them to infer the mechanisms involved. Team Edwards will also manipulate activity directly and determine how it interacts with known genes to produce degeneration.

Hypothesis: Team Edwards hypothesizes that abnormalities in neural activity do not simply reflect PD but actually cause the disease. Researchers’ lack of knowledge about the role of neural activity in Parkinson’s makes it difficult to understand how other, identified factors contribute to disease.

Study Design: Team Edwards will use two models of PD, one based on over-expression of the pathogenic protein alpha-synuclein and the other based on a direct increase in activity. The strategy is to (a) identify the earliest events along the pathway to degeneration and to (b) correlate these with the selective vulnerability of particular neurons to PD. These approaches will reveal the processes specifically affected by PD. Team Edwards will also determine how neural activity intersects with factors previously implicated in PD, providing a foundation to understand how they cause degeneration.

Impact on Diagnosis: With greater understanding around the onset of disease, Team Edwards can further investigate how genetic and environmental factors conspire to produce PD. This will open entirely new areas to arrest and prevent the underlying degeneration.

Leadership
Robert Edwards, MD
Coordinating Lead PI

Robert Edwards, MD

University of California at San Francisco
Zayd Khaliq, PhD
Co-Investigator

Zayd Khaliq, PhD

National Institutes of Health
Ken Nakamura, MD, PhD
Co-Investigator

Ken Nakamura, MD, PhD

Gladstone Institutes
Alexandra Nelson, MD, PhD
Co-Investigator

Alexandra Nelson, MD, PhD

University of California at San Francisco
Talia Lerner, PhD
Co-Investigator

Talia Lerner, PhD

Feinberg School of Medicine at Northwestern University
Haru Yamamoto, BA
Project Manager

Haru Yamamoto, BA

University of California at San Francisco

Project Outcomes

By identifying the earliest changes leading to degeneration, the physiology will indicate mechanisms involved in disease onset. View Team Outcomes.

Team Outputs

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Overall Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of November 2023. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific theme.

Impact

Theme

Featured Output

Below is an example of a research output from the team that contributes to the ASAP mission of accelerating discoveries for PD.

Therapeutic deep brain stimulation disrupts movement-related subthalamic nucleus activity in parkinsonian mice

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinson’s disease (PD), but its underlying therapeutic mechanisms remain unclear. Team Edwards used electrical artifact-free GCaMP fiber photometry during STN DBS in a Parkinson’s mouse model and observed changes in activity that were sufficient to relieve motor symptoms. These findings suggest that STN DBS exerts its therapeutic effect through the disruption of movement-related STN activity, providing further insight into optimizing PD treatments and establishing an approach for investigating DBS in other neuropsychiatric conditions.

Team Accolades

Members of the team have been recognized for their contributions.

Other Team Activities

  • Updates will be posted when available.

In the News

  • The team is hard at work and will share outcomes when available.

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