THALAMIC ACTIVITY IN PARKINSONISM (UDALL CENTER, PROJECT #2)

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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. Neurosurgical interventions, such as deep brain stimulation (DBS) of the internal pallidal segment (GPi) or the subthalamic nucleus (STN), or GPi lesions, are helpful in patients with Parkinson's disease. DBS and lesioning procedures produce contrasting effects on their immediate brain targets: Lesions reduce the output of the lesioned nucleus, while electrical stimulation may lead to local neuron inhibition, and stimulation of efferent or afferent fibers. Despite these differences, lesions and stimulation have remarkably similar clinical and behavioral effects, perhaps because they lead to similar effects in nuclei further downstream, particularly in the thalamus, the recipient of a dense projection from the basal ganglia. Previous studies have suggested that thalamic neurons show an increased tendency to fire in bursts and to generate oscillatory patterns of activity in parkinsonism, which may act to disrupt thalamocortical interactions, and may be involved in the generation of parkinsonian signs. To test whether lesions and DBS aimed at GPi or STN have the same or different effects on thalamic firing we examine the effects of GPi inactivation, and of electrical stimulation of the STN or GPi on neuronal activities, GABA levels, and morphological aspects of the synaptic pallidothalamic interactions in parkinsonian monkeys. These studies have just started, and we are currently doing the first studies to examine the effects of STN stimulation on thalamic activities. A better understanding of the downstream effects of lesions and stimulation may help us to define more specific neurosurgical or pharmacological therapies, or therapies that combine pharmacologic treatments with neurosurgical interventions.