SYNAPTIC CONTROLOF PALLIDAL ACTIVITY

苍白球位于基底节连接的重要部位，被认为在基底节的生理和病理生理学中起着关键作用。我们和其他人的最新结果表明，苍白球神经元在不同的病理生理条件下会改变其放电频率和模式。我们和其他人所做的一个戏剧性观察是，化学阻断丘脑底核(STN)在苍白球神经元中诱导了非常缓慢的振荡活动，即长活跃和长静止期的交替发生。我们的主要工作假设是，苍白球的缓慢振荡可能是由于突触输入和苍白球神经元膜特性的改变。本研究的目的是研究正常情况下和摘除STN后苍白球的突触输入和膜特性。大鼠脑片制备中的全细胞记录技术和觉醒猴的整体记录与局部给药技术将被用于解决以下两个具体目标。AIM-1将验证这一假设，即在正常清醒动物的苍白球神经元中观察到的高频单位活动是由于持续的谷氨酸和持续的GABA能突触输入的协同激活。AIM-2将验证这一假说，即移除谷氨酸能STN-苍白球传入不仅通过移除谷氨酸能传入改变苍白球神经元的放电频率和模式，而且还通过诱导突触传入和膜特性的可塑性改变来改变苍白球神经元的放电频率和模式。这项研究的意义在于，所获得的结果将1)促进我们对梅毒的生理特性的了解，2)揭示患有基底节疾病的患者的梅毒可能发生的变化。这些发现可能有助于形成新的、侵入性较小的治疗基底节疾病的策略。

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.