DOPAMINERGIC & GABAERGIC ACTIONS OF PALLIDAL DISCHARGE

我们目前的目标是确定（1）多巴胺通过D1和D2受体对苍白球内外段神经元的紧张性和相位性放电的作用，以及（2）纹状体GABA对纹状体输出神经元的作用。 在三只猴子中，通过植入PAN-PVC管将药理学试剂应用于纹状体。 总之，Dubach博士开发的技术导致管路沿着壳核外侧部分的弯曲纵向轨迹准确放置。 Eaton博士使用HPLC显示，体外薄壁管中多巴胺的回收率几乎为100%。 应用GABAA拮抗剂荷包牡丹碱直接进入壳核通过植入管导致局部运动障碍和苍白球神经元放电的间歇爆发发作。 爆发之前通常会有短暂的停顿，但并不总是如此。 间歇/爆发发作不是在随机时间发生的，而是在不同方向的运动期间的不同特定时间发生的。 我们对数据的解释表明，被阻断的抑制可能是由与发送到纹状体输出神经元的信号相同或相关的运动信号以前馈方式驱动的。 我们已经成功地应用了D1选择性拮抗剂SCH 23390和D2选择性拮抗剂raclopide，同时监测苍白球神经元的行为和记录。 在高浓度下，类似于其他人注射到大脑皮层中的药物，这两种药物都会中断行为，并且在SCH 23390的情况下，会引起嗜睡。我们以十倍的步骤降低了浓度两次，发现行为中断的时间和恢复行为的洗脱时间都是剂量依赖性的。 我们目前正在分析同时记录的苍白球神经元的行为和活动，以确定随着药物作用的开始和结束，任务的不同方面和相关的苍白球放电如何变化。

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.