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. This project aims at studying the localization, functions and potential antiparkinsonian benefits of GABAB receptor modulation in monkeys. To achieve these goals we use various immunocytochemical and functional approaches that include high resolution immunogold procedures at the electron microscopic level, microdialysis techniques, in vivo single unit recording in rhesus monkey basal ganglia and behavioral testing in parkinsonian monkeys. Over the past year, we demonstrated that GABA-B receptors are widely expressed pre- and post-synaptically in the monkey globus palidus and subthalamic nucleus. Furthermore, we have also shown that local intracereberal injection of both GABA-A and GABA-B receptor agonists has strong inhibitory effects in the monkey globus pallidus. In addition, we provided clear evidence that increased GABA spillover in the globus pallidus, through blockade of GABA transporters play an important role in mediating inhibitory influences towards pallidal neurons in monkeys. Together, these functional and anatomical data emphasize the importance of extrasynaptic GABA receptors in controlling neuronal activity in the basal ganglia. Ongoing experiments are in progress to assess the role of extrasynaptic GABA receptors in parkinsonians.
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