Team Surmeier

Study Rationale: Parkinson’s disease (PD) begins decades before it compromises the ability to move about in the world and sleep through the night. Understanding how the dysfunction of brain circuits begins and then evolves to cause difficulty in moving and sleeping will allow researchers to diagnose PD earlier—increasing the chances of halting disease progression—and to better treat the disease once it appears.

Hypothesis: The progressive damage to dopamine-releasing neurons results in staged disruption of neural circuits in larger and larger parts of the brain, ultimately leading to both motor and sleep deficits characteristic of PD.

Study Design: Team Surmeier’s plan is to study a new genetically engineered mouse model that manifests a progressive, levodopa-responsive parkinsonism. Importantly, this mouse faithfully reproduces the human staging of pathology in key brain circuits. Using the most advanced methods available for studying and manipulating genetically defined brain circuits, the causal linkage between circuit dysfunction and motor and sleep behavior will be determined. 

Impact on Diagnosis: A better understanding of how the circuit dysfunction underlying PD is staged should allow earlier diagnosis—enhancing the potential benefit of disease-modifying therapies—and better treatment strategies for later-stage patients.