This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Cortical inputs reach basal ganglia structures, which project back to thalamus and cortex. Due to the lack of the neurotransmitter dopamine synchronized oscillatory and non-oscillatory activity appear in the basal ganglia which can be measured with local field potential (LFP) recordings. In our primate experiments, we study recordings of LFP changes that are associated with the induction of Parkinsonism by treatment with the neurotoxin MPTP. We also study the local effects of dopaminergic drugs on neuronal synchrony in the basal ganglia nuclei, using a microdialysis/LFP recording probe which allows us to assess the effects of drugs, applied locally via reverse microdialysis, on LFPs in the vicinity of the probe.In this funding period we continued studies of LFP changes produced through blockade of receptors for the inhibitory neurotransmitter GABA in the striatum, and their modulation through the local application of dopamine receptor blockers. GABA receptor blockade induced recurrent large LFP events which were not directly synchronized to neuronal activity in the immediate vicinity of the LFP probe, therefore likely reflecting synchronous synaptic inputs instead. Experiments concerning the effects of dopamine receptor blockers on LFPs, and the ability of these drugs to modulate the LFP events produced by GABA-receptor blockade were done in two monkeys and showed a trend of LFPs to increase with dopamine receptor blockade. In addition, we have completed our studies of task-related changes of striatal and pallidal LFPs in one animal, and have trained a second one. Finally, we have begun recordings of LFPs in an animal that will undergo MPTP treatments in the upcoming funding period, so that gradual Parkinsonism-related changes in basal ganglia LFPs can be monitored. These experiments will add to our understanding of the temporal (and causal) relationship between LFPs and behavioral abnormalities in Parkinsonism.
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