THE THALAMOSTRIATAL SYSTEM IN PRIMATES

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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. The anatomical organization of the thalamostriatal system has been a topic of major interest for Dr Smith and colleagues for the past many years. During the previous funding period, they have expanded their electron microscopic anatomical studies to various thalamic nuclear groups that contribute to striatal innervation, examined the synaptic plasticity of the thalamostriatal system in animal models of Parkinson's disease and looked at the electrophysiological effects of thalamic stimulation upon striatal activity in rhesus monkeys. The main findings obtained in these studies are summarized as follows: 1) Their ultrastructural data revealed the existence of dual thalamostriatal systems based on thalamic origin, synaptic targets in the striatum and extent of relationships with the cerebral cortex and striatum; a system that originates from the centre median and parafascicular nuclei (CM/Pf), which targets preferentially dendritic shafts of striatal neurons and provide only minor inputs to the cerebral cortex, and a second system, which originates from other thalamic nuclei, targets almost exclusively dendritic spines of striatal neurons, provides significant inputs to specific cortical areas and send axon collaterals to functionally related regions of the striatum. 2) They demonstrated that both the glutamatergic corticostriatal and thalamostriatal systems undergo complex plastic changes in their ultrastructural organization in the nonhuman primate model of Parkinson's disease. These changes most likely underlie differential electrophysiological properties of these two glutamatergic systems in primates, and contribute to alterations of striatal glutamatergic transmission in Parkinson's disease. Together, these findings provide a solid foundation for a deeper understanding of the functional organization of the thalamostriatal networks in normal and parkinsonian conditions. This information is critical for the interpretation and refinement of the use of high frequency stimulation of caudal intralaminar nuclei as new treatment of movement disorders including Tourette's syndrome and Parkinson's disease.