Study Rationale:
Multiple brain structures work together to coordinate movement. We have found a new pathway that modulates movement through a brainstem structure that dies in Parkinson’s disease (PD) called the pedunculopontine nucleus (PPN). Deep brain stimulation (DBS) has been targeted to the PPN in PD patients to alleviate gait and balance symptoms. However, this approach has met with variable success. It is not yet clear why these results are so variable, but it may be due to the many different neuron types and neural pathways that run through this structure. Understanding these connections is critical for developing precise DBS location targeting.
Hypothesis:
This project will test the hypothesis that inputs the brainstem will differentially promote and inhibit movement depending on which PPN neuron types they modulate.
Study Design:
We will stimulate specific pathways to the brainstem in pre-clinical models and measure the amount and type of movement this stimulation causes. We have cutting-edge tools that allow use to selectively stimulate very specific subcircuits within the brainstem to precisely isolate the importance of each specific neuron type in the generation or inhibition of movement. We will also take a complimentary approach and measure the natural movement of pre-clinical models while recording brainstem neural activity. This will form a complete picture of the circuits that promote and inhibit movement.
Impact on Diagnosis/Treatment of Parkinson’s disease:
This project represents an important pre-clinical step in understanding fundamental brain circuitry governing movement. Brainstem DBS therapy has been ineffective because we do not yet understand which brainstem circuits promote and inhibit movement. This project will lay the groundwork for developing more precise DBS therapies.