Study Rationale: Individuals with Parkinson’s disease (PD) can show a variety of symptoms, including: resting tremors, alterations in directed hand movements, and treatment-induced dyskinesias; loss of facial expression; stooped posture and, ultimately, problems with standing as well as freezing of gait; autonomic dysfunction, particularly drops in blood pressure and constipation. To understand the origins of these symptoms and develop appropriate treatments, we need to understand the basic wiring diagrams for the neural control of hand movement, facial expression and axial body control and autonomic function. In this project, we will determine the neural networks that control an example of each system.
Hypothesis: Understanding the wiring diagrams that underlie the brain-body connections will provide an essential foundation for investigating basic mechanisms of disease initiation and progression and will facilitate the development of new treatments to ameliorate the most troubling symptoms of the disease.
Study Design: We will use the transport of rabies virus between connected neurons to generate detailed wiring diagrams for four neural networks that are directly attacked or functionally affected by PD. For hand movement, we will study the muscle that drives the extension of the fingers. For facial expression, we will study the frontalis muscle, which is used to express emotions. For axial body control, we will study the spinalis muscle that is essential for upright posture. For autonomic function we will study the celiac ganglion, which innervates multiple internal organs, including the esophagus, stomach, pancreas, spleen, kidneys, liver, and small intestine.
Impact on Diagnosis/Treatment of Parkinson’s disease: The wiring diagrams of these networks will provide an essential foundation for investigating basic mechanisms of disease initiation and progression. They also are critical for developing new treatments to ameliorate the most troubling symptoms of the disease.
Next Steps for Development: Our wiring diagrams can be used to explore whether blocking a particular pathway impedes disease progression and whether the neural networks that control body posture differ from those involved in limb movements. The results could facilitate identification of alternative targets for deep brain stimulation to treat posture, balance and other PD symptoms.