DOPAMINERGIC & GABAERGIC ACTIONS OF PALLIDAL DISCHARGE

我们目前的目标是确定(1) 多巴胺通过D_1和D_2受体对张力性和时相放电的影响 苍白球外节和内节的神经元，以及(2) 纹状体GABA对纹状体输出神经元的影响。药理作用 药剂已经通过植入聚氯乙烯应用于纹状体。 插进三只猴子的管子。总而言之，这项由Dr。 Dubach使油管沿着弯曲的方向精确放置 壳核外侧部分的纵向轨迹。Dr。 伊顿使用高效液相色谱显示多巴胺几乎100%的恢复 试管中的较薄管壁。GABAA算法的应用 拮抗剂荷包牡丹碱通过植入直接进入壳核 管子导致局限性运动障碍和停顿-爆发性发作 苍白球神经元的放电。爆发通常是，但不是 总是，在此之前会有短暂的停顿。停顿/爆发的剧集没有 发生在随机时间，但在不同的特定时间 向不同方向移动。我们对数据的解读是为了表明 被阻止的抑制可能是在一种 前馈方式，通过与之相同或相关的电机信号 发送到纹状体输出神经元的信号。我们已经应用了 D_1选择性拮抗剂SCH23390和D_2选择性拮抗剂 在监控行为和记录时成功使用raclopide 苍白球神经元。在高浓度下，与注射的类似 通过其他人进入大脑皮层，两个代理都中断了行为，并在 SCH23390的案例引起了人们的昏昏欲睡。我们已经降低了 两次集中在十倍的步子里，发现 行为中断和恢复行为的冲刷时间是 两者都有剂量依赖性。我们目前正在分析行为和 同时记录的苍白球神经元的活动以确定 任务的不同方面和相关的苍白球放电 随着药物效应的开始和结束而改变。

Our current objectives are to determine (1) the actions of dopamine via D1 and D2 receptors on tonic and phasic discharge of neurons in external and internal pallidal segments, and (2) the effects of striatal GABA on striatal output neurons. Pharmacological agents have been applied to the striatum through implanted PAN-PVC tubing in three monkeys. In all, the technique developed by Dr. Dubach resulted in accurate placement of the tubing along a curved longitudinal trajectory in the lateral portion of the putamen. Dr. Eaton has used HPLC to show almost 100% recovery of dopamine across the thinner-walled tubing in vitro. Application of the GABAA antagonist bicuculline directly into the putamen through the implanted tubing resulted in localized dyskinesias and pause-burst episodes of discharge in pallidal neurons. The bursts were usually, but not always, preceded by brief pauses. The pause/burst episodes did not occur at random times, but at different particular times during movements in different directions. We interpret the data to indicate that the inhibition being blocked was driven, probably in a feed-forward manner, by motor signals that were the same as or related to signals sent to striatal output neurons. We have applied the D1-selective antagonist SCH23390 and the D2-selective antagonist raclopide successfully while monitoring behavior and recording from pallidal neurons. In high concentrations, similar to those injected by others into the cortex, both agents interrupted behavior and, in the case of SCH23390, caused drowsiness. We have reduced the concentration twice in tenfold steps and found that the time to behavioral interruption and the washout time to restore behavior are both dose-dependent. We currently are analyzing both the behavior and the activity of concurrently recorded pallidal neurons to determine how different aspects of the task and the related pallidal discharge changed as the drug effect began and ended.