University of Virginia Health System

The principal focus in the laboratory is on the cellular mechanisms of neuropharmacologic actions in the striatum. The current emphasis is on interactions of dopamine and acetylcholine in regulating striatal output neurons because of the relevance of these transmitters to the pathophysiology and treatment of neurodegenerative disease. Dr. Harrison and colleagues have used retrogradely transported neurotoxins or "suicide transport" agents to produce selective lesions of striatonigral and striatopallidal neurons to examine localization and regulation of neurotransmitter receptors. With this technique, they have demonstrated selective localization of specific dopamine and muscarinic receptor subtypes to striatonigral neurons using receptor autoradiography and in situ hybridization. In a collaborative project, investigators have examined dopaminergic regulation of acetylcholine release in the striatum using striatal slices and acutely dissociated striatal neurons. With the same technique, they are now studying selective muscarinic receptor actions on striatal output neurons and their interactions with dopaminergic receptor effects. In addition, the laboratory has begun work to characterize effects of a selective immunotoxin lesion of cholinergic interneurons.