Final Activity Report Summary - MOVEMENT DISORDERS A (The implications and interactions of basal ganglia and cerebellum in movement disorders) First microdialysis experiments were conducted in anaesthetised naive rats to assess the effect of a microinjection with the GABA antagonist bicuculline in the dentate nucleus, a main output nucleus of the cerebellum, on glutamate and GABA release in the centrolateral nucleus and the dorsal striatum. This microdialysis approach was completed by the simultaneous detection of DA and the metabolites 3,4-dihydroxyphenylacetic and homovanillic acid in the dorsal striatum. The preliminary results show that an inhibition of the dentate nucleus does not modulate the release of glutamate and GABA in the centrolateral nucleus and the dorsal striatum, while DA transmission in the dorsal striatum is increased. This suggests that the cerebellar output nuclei might modulate the activity of nigrostriatal dopamine neurons although the implicated pathways remain yet unknown. Interestingly, these nigrostriatal dopamine neurons undergo a progressive degeneration in PD suggesting that the cerebellum could be implicated in the onset of PD symptoms or compensatory mechanisms in the course of the disease. In a second part of the project and in collaboration with the research group of Professor A. Kupsch, a microstimulator has been developed that allows the application of continuous high frequency stimulation in rats for several weeks. This device will be mandatory in the future to determine mechanisms of action of high frequency stimulation implicating BG and cerebellum.
