Identification of Axon Guidance Molecules Relevant to the Midbrain Dopaminergic System

In Parkinson's patients a substantial number of dopaminergic neurons necessary for proper motor control have died, leading to dyskinesias that make it difficult to walk and talk. A promising approach to alleviating the symptoms of Parkinson's disease is to transplant healthy dopaminergic neurons into the brain of these patients. The success of this procedure, however, has been variable, and may be limited in part by the ability of the transplanted neurons to find their correct targets in the brain. Within the brain, neurons have axonal extensions that project to other neurons and the fidelity of this "wiring" is what gives the brain its enormous capacity to sense, integrate and digest information and to command and execute movement. "Miswirings" can be worse than no wiring and it is therefore essential that the newly transplanted dopaminergic neurons find their correct targets. Through a series of anatomical, genetic and biological approaches we will identify signals that normally guide dopaminergic axons to their targets in hopes that these signals can be used in transplant patients to assist the transplanted neurons in making successful new wirings