This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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 appears 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. We have continued our experiments of LFP changes in parkinsonian animals. The studies are carried out in monkeys that are undergoing a slow course of MPTP treatment, combined with monitoring of parkinsonian signs. While we are currently recording in the third animal in this series, a fourth animal is being prepared for the studies. The results of these experiments (as well as those of systemic dopamine receptor antagonist injections) demonstrate that acute dopamine receptor blockade is not sufficient to produce significant LFP changes in the basal ganglia, while chronic dopamine depletion produces changes in oscillatory LFP properties. These findings, together with the emerging evidence of anatomical differences between acute and chronic dopamine depletion models, suggest that dopamine loss alone is not sufficient to alter oscillations, and that secondary anatomical changes may have to occur to produce changes in the oscillatory properties. These findings further clarify the role of dopaminergic and non-dopaminergic changes in the basal ganglia in parkinsonism. A thorough understanding of the relationship between LFP changes and parkinsonism may help us to develop predictive algorithms that can be used as control signals in on-demand deep brain stimulation devices for parkinsonian patients.
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