Our long term research goal is to understand the functional role of the basal ganglia in motor control. Our efforts in the past few years were directed mainly to reveal the connections and the functions of the subthalamus. Our findings indicated clearly that the subthalamus receives excitatory inputs from the cortex and sends excitatory outputs to most of the nuclei in the basal ganglia. It was also made evident that the cortex and the basal ganglia output nuclei are connected by two parallel pathways having opposite output signals (i.e.. excitatory vs. inhibitory). Recent literature and our findings have led me to form an hypothesis about the basic role of the globus pallidus in the regulation of neuronal activity of the basal ganglia. The hypothesis is that the activity of pallidal, neurons is controlled by the converged inputs through the parallel pathways originating from the cortex and connected through the neostriatum and the subthalamus and that the pallidal inhibitory outputs regulate the entire basal ganglia activity.
The aims of this proposal are: (1) to determine the nature of pallidal projections to the neostriatum and substantia nigra, (2) to determine whether tonic pallidal synaptic outputs regulate activity of basal ganglia nuclei and whether the globus pallidus provides feed forward or feed back control on the flow of cortically derived signals in the basal ganglia, (3) to identify the origin of the slow and powerful excitations which were seen in pallidal neurons after cortical and subthalamic stimulation, and (4) to characterize membrane properties of pallidal neurons which regulate their firing behaviors. The main techniques to be used in the studies using anesthetized rats include intracellular recording and labeling, unit recording, electrical stimulation, chemical stimulation, chronic lesion, anterograde and retrograde labeling, and immunostaining for neuroactive substances. Intracellular recordings in brain slices will be performed to study ionic currents involved in the activity of globus pallidus neurons. Both current clamp and voltage clamp recordings will be used in these studies. This study is essential in the understanding of the function of the basal ganglia and the etiology of basal ganglia disorders.
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