We hypothesize that enhanced gap junction communication (GJC) plays an unheralded and important role in the neural mechanisms underlying levodopa-induced dyskinesia (LID). Gap junctions are a special type of junction between cells which mediate cell to cell communication, joining one cell directly to another, such that there is a to and fro communication between the cells. The classical and more numerous chemical synapses mediate one way communication between brain cells with the release of a neurotransmitter (e.g. dopamine) from one cell onto a receiving cell. In the brain, GJC complements signaling by classical synaptic transmission and impacts significantly on neuronal activity and synchrony. Several lines of evidence support a role for enhanced GJC in LID, but to date there have been no studies on the role of GJC in the generation of dyskinesia in well-validated animal models of LID. The project will employ electrophysiological, molecular biological and behavioural pharmacological techniques to identify abnormalities of GJC and the role they play in generating dyskinesia in both rodent and the MPTP-lesioned primate models of Parkinson's disease. The final phase of the project will assess the potential of modulating GJC as a treatment for LID.