Background pattern of a brain with neural connections

Team Cragg

Mapping the modulatory landscape governing striatal dopamine signaling and its dysregulation in Parkinson’s disease

2021-Present

The axons of nigrostriatal dopamine neurons are colossal structures harboring unexplored biology that determines the function and dysfunction of striatal circuits. The neuromodulator networks interacting with dopamine axons are in a powerful position to rescue or exacerbate dopamine dysfunction in Parkinson’s disease (PD) yet are surprisingly poorly understood. We will exploit state-of-the-art tools to meet the pressing need to define the neuromodulators, cells and circuits, neuronal and non-neuronal, that act on and through axons of vulnerable dopamine neurons. We propose that distinct neuromodulator networks become unbalanced in vulnerable circuits during PD progression, and will offer new avenues for translational benefit.

Tags
Alpha-synuclein GBA (Glucocerebrosidase)

Leadership

Stephanie Cragg

Stephanie Cragg

Lead PI (Core Leadership)

Mark Howe

Mark Howe

Co-PI (Core Leadership)

Peter Magill

Peter Magill

Co-PI (Core Leadership)

Konstantinos (Dinos) Meletis

Konstantinos (Dinos) Meletis

Co-PI (Core Leadership)

Richard Wade-Martins

Richard Wade-Martins

Co-PI (Core Leadership)

Cláudia Mendes

Cláudia Mendes

Project Manager

Project Highlights

Distinct spatially organized striatum-wide acetylcholine dynamics for the learning and extinction of Pavlovian associations

Striatal acetylcholine (ACh) signaling is thought to counteract reinforcement signals, promoting extinction and behavioral flexibility. Changes in striatal ACh signals have been reported during learning, but how ACh signals for learning and extinction are spatially organized to enable region-specific plasticity is unclear. We used array photometry in mice to reveal...

Contributions

Here is an overview of how this team’s article findings have contributed to the PD field as of June 2025. There are two different categorizations of these contributions – one by impact to the PD community and a second by scientific category.

Impact

Category

Accolades

Members of the team have been recognized for their contributions.

Team Cragg

Open Science Champions

Peter Kilfeather, Natalie Doig, Mai-Anh Vu, Cláudia Mendes

Awards

2023 Collaborative Meeting

COSA Prize Winners 2024

Network Spotlights

Cláudia Mendes

In the News

Updates will be posted when available.

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