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.The basal ganglia are part of larger circuits. Cortical inputs reach striatum and subthalamic nucleus (STN), and are transmitted via external and internal pallidal segments (GPe, GPi, resp.) and substantia nigra pars reticulata to influence the activity of thalamocortical neurons. The function of this circuitry is abnormal in Parkinson's disease. One of the most salient abnormalities is the appearance of synchronized oscillatory activity which can be measured with local field potential (LFP) recordings. Studies in humans, using implanted deep brain stimulation (DBS) electrodes to record LFPs, have suggested that high-amplitude, low-frequency oscillations develop in parkinsonism. Uncertainties persist, however, regarding the temporal and causal relationship between circuit synchrony and parkinsonism, as well as the location at which dopamine loss exerts its synchronizing effects.We studied the development and long-term stability of LFP characteristics of parkinsonism in MPTP-treated primates, using chronically implanted LFP electrodes throughout striatum, GPe, GPi and STN, combined with pharmacologic manipulation of dopaminergic transmission (aim 1). We also studied the local effects of dopaminergic drugs on neuronal synchrony in these 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. These studies assessed drug-effects on spontaneous LFP production (aim 2), and on event-related LFP fluctuations in motor tasks (aim 3). These experiments helped to better understand the origin(s) and functional significance of neuronal ensemble activity in parkinsonism. This knowledge was useful in the development of antiparkinsonian treatments targeting synchronous basal ganglia activity, and developed criteria to detect the presence of parkinsonism in LFP signals from the basal ganglia. Conceivably, such criteria could be used in DBS devices to trigger 'on-demand' stimulation.
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