SYNAPTIC CONTROLOF PALLIDAL ACTIVITY

$217,864P50FY2005NSNIH

Northwestern University, Evanston IL

Investigators

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Abstract

The globus pallidus is located at the strategically important locus of the basal ganglia connections and is considered to play a key role in the physiology and pathophysiology of the basal ganglia. Our recent results and those of others suggested that the pallidal neurons change their firing rate and pattern under various pathophysiological conditions. One dramatic observation made by us and others was that a chemical blockade of the subthalamic nucleus (STN) induced a very slow oscillatory activity, an alternating occurrence of long active and long silent periods, in pallidal neurons. Our main working hypothesis is that the slow oscillation of the pallidum might be due to alterations in the synaptic inputs and the membrane properties of the pallidal neurons. The goal of proposed study is to characterize the synaptic inputs and the membrane properties of the pallidum under normal conditions and after removal of the STN. The whole-cell recording technique in rat brain slice preparations and the unitary recording combined with local drug application techniques in awake-monkeys will be used to address the following two specific aims. Aim-1 will test the hypothesis that high-frequency unitary activity observed in pallidal neurons in normal awake-animals is due to the concerted activation of sustained glutamatergic and sustained GABAergic synaptic inputs. Aim-2 will test the hypothesis that the removal of the glutamatergic STN-pallidal inputs alter the firing rate and the pattern of pallidal neurons not only by the removal of glutamatergic inputs but also by inducing plastic changes of synaptic inputs and membrane properties. The significance of the proposed study is that the results obtained will 1) advance our knowledge of the physiological properties of the pallidum and 2) reveal changes that might occur in the pallidum of patients suffering from basal ganglia diseases. These finding might contribute to the formation of new, less invasive, therapeutic strategies for basal ganglia diseases.

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