DOPAMINERGIC & GABAERGIC ACTIONS OF PALLIDAL DISCHARGE

多巴胺能

• 批准号: 6277537
• 负责人: MARJORIE E ANDERSON
• 金额: $ 7.23万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277537
• 关键词: Mammalia; Primates; cognition; musculoskeletal system; nervous system; rehabilitation

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.

我们当前的目标是确定 (1) 的行动 多巴胺通过 D1 和 D2 受体对强直和阶段性放电 外部和内部苍白球节段的神经元，以及（2） 纹状体 GABA 对纹状体输出神经元的影响。 药理作用 通过植入 PAN-PVC 将药剂应用于纹状体 三只猴子的管子。 总而言之，博士开发的技术。 杜巴赫 (Dubach) 成功地将管道沿着弯曲的方向准确放置 壳核外侧部分的纵向轨迹。 博士。 伊顿使用 HPLC 显示多巴胺几乎 100% 回收 体外的薄壁管。 GABAA的应用 拮抗剂荷包牡丹碱通过植入的直接进入壳核 管道导致局部运动障碍和暂停爆发发作 苍白球神经元放电。 爆发通常是，但不是 总是，之前有短暂的停顿。 暂停/突发事件没有 发生在随机时间，但发生在不同的特定时间 不同方向的运动。 我们解释数据以表明 被阻断的抑制是被驱动的，可能是在 前馈方式，通过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 D1-选择性拮抗剂 SCH23390 和 D2-选择性拮抗剂 雷氯必得成功监测行为并记录 苍白球神经元。 高浓度，类似于注射的浓度 由其他智能体进入皮质，两种智能体都会中断行为，并且 SCH23390 的情况下，导致嗜睡。 我们减少了 以十倍的速度集中两次，发现时间 行为中断和恢复行为的清除时间是 两者均呈剂量依赖性。 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 任务的不同方面以及相关的苍白球放电如何 随着药物作用开始和结束而改变。