Study Rationale: Over time, people with Parkinson’s disease (PD) develop problems with their ability to walk that can cause serious injuries and curtail their independence. Mice with a particular genetic modification develop similar locomotor issues and show brain changes akin to those seen in people with PD. We will use microscopic and genetic techniques to explore how these movement deficits arise and evolve. We will then identify the areas of the mouse brain for which stimulation will slow these changes and prevent the development of motor problems.
Hypothesis: We hypothesize that stimulating the brain region that is overly active before gait problems appear can delay the onset of these issues and render them less severe.
Study Design: First, we will use state-of-the-art microscopic and genetic techniques to monitor activity across the entire mouse brain to learn how walking problems develop in the genetically-modified mice. We will identify two brain regions that are overly active just before these issues arise and assess how switching off and on the neurons in these areas affects gait. Finally, we will examine how applying continuous electrical stimulation, similar to that used clinically, to these regions influences the appearance and severity of the walking problems.
Impact on Diagnosis/Treatment of Parkinson’s disease: Identifying brain regions that respond to stimulation in mice could lead to a new treatment for improving symptoms and alleviating motor deficits, particularly those involving gait, in people with PD. Such therapy would lead to an improvement in quality of life.
Next Steps for Development: We will directly follow this project by testing whether electrical stimulation of the selected brain parts in people with PD is safe and whether it influences the appearance and severity of problems with walking.