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. Two main sets of experiments have been achieved in this project over the past year. In a first series of studies we analyzed the sub-synaptic localization of GABAB R1 and GABAB R2 in the monkey CM/Pf complex. Four main conclusions can be made from these data: (1) Both CM and Pf are enriched in GABAB R1 and R2 immunoreactivity, (2) Both receptor subtypes are mainly expressed on the plasma membrane, though a significant pool of GABAB R2 is also found intracellularly in dendrites of CM/Pf neurons, (3) The vast majority of post-synaptic immunoreactivity for both receptor subtypes is expressed extrasynaptically or peri-synaptic to asymmetric glutamatergic synapses, and (4) A significant pool of pre-synaptic receptors is expressed in pre-terminal axons and glutamatergic terminals. In brief, GABAB receptors are located to sub-serve complex pre- and post-synaptic functions that largely rely on extrasynaptic neuronal communication likely mediated by spillover of neurotransmitter in the primate CM/Pf complex. In a second series of experiments, we studied the synaptic organization of glutamatergic afferents to the rat and monkey striatum using vGluT1 and vGluT2 as specific markers of these two pathways. We also examined changes in the synaptology and expression of these proteins in the monkey model of Parkinson?s disease. Two main conclusions can be drawn from these observations: 1) The synaptology of the thalamostriatal system is highly heterogeneous and specific to its nuclear origin and striatal compartmentalization 2) There is a significant change in the relative density of vGluT1-containing terminals in the striatum of MPTP-treated parkinsonian monkeys, suggesting that changes in function of the corticostriatal system represent a key features of Parkinson?s disease pathophysiology in primate
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