This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cortical inputs reach basal ganglia structures, which project back to thalamus and cortex. Under parkinsonian conditions, synchronized oscillatory activities appears in the basal ganglia which can be measured with local field potential (LFP) recordings. We are currently recording in two animals. One of them has received a large cumulative dose of MPTP, given slowly over several months, and has developed parkinsonism, while MPTP treatments in the other animal will start soon (after completion of studies in the normal state). We also examine effects of dopamine receptor antagonist injections in the normal state, and agonist treatment in parkinsonism. We found that only chronic dopamine depletion, but not acute dopamine receptor blockade, produces significant LFP changes. Together with anatomical evidence, these findings suggest that morphological changes secondary to chronic dopamine loss are necessary for changes in oscillations. Our results demonstrate that parkinsonism signs are manifest without LFP changes, questioning the causative role of pathological oscillations. A thorough understanding of the relationship between LFP changes and advanced parkinsonism may also advance ongoing efforts to use LFP signals as control signals for on-demand deep brain stimulation devices for parkinsonian patients. In collaborative studies, we have continued our exploration of this aspect in human patients
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