Evidence for functional differences between entopeduncular nucleus and substantia nigra: Effects of APV (DL-2-amino-5-phosphonovaleric acid) microinfusion on reaction time performance in the rat
Evidence for functional differences between entopeduncular nucleus and substantia nigra: Effects of APV (DL-2-amino-5-phosphonovaleric acid) microinfusion on reaction time performance in the rat
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DOI：
10.1111/j.1460-9568.1996.tb01341.x
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发表时间：
1996-09-01
影响因子：
3.4
通讯作者：
Amalric, M
中科院分区：
文献类型：
--
作者：
Baunez, C;Amalric, M
最近发现，丘脑底核（STN）兴奋性氨基酸输出的过度活跃是帕金森病中黑质纹状体多巴胺能变性引起的一系列后续破坏之一。 STN 的兴奋性谷氨酸输出结构的各自贡献[即然而，苍白球（GP）、内脚核（EP）和黑质网状部（SNr）]对运动控制的作用尚不清楚。为了进一步研究通过这三种结构中的 NMDA 受体亚型进行谷氨酸传递的功能，在执行反应时间任务的大鼠中测试了竞争性受体拮抗剂 DL-2-氨基-5-磷酸戊酸 (APV) 离散局部输注至 EP、GP 和 SNr 的效果。将 APV 双边输注到 STN 的不同输出结构中，会不同程度地损害经过训练的大鼠的表现，这些大鼠在视觉刺激出现后在一定时间内释放杠杆以获得食物奖励。研究发现，将 APV（0.25 和 0.5 μg/0.5 μl）输注到 SNr 中会诱发行为缺陷，其特征是过早释放杠杆的次数急剧增加，平均反应时间缩短。相反，发现将0.25μg剂量的APV输注到GP或EP中会诱发运动启动缺陷，其特征是延迟反应数量增加（时限后杠杆释放）和平均反应时间增加。剂量为 0.5 μg 时，除了先前的运动障碍外，还出现了过早的反应缺陷。有趣的是，当 APV 同时注入同一只动物的 GP 和 SNr 时，行为效果往往与单次注入 SNr 后观察到的行为效果相似。总而言之，这些结果表明，起源于 STN 水平的三个主要输出途径的不同功能权重是SNr 中 NMDA 受体阻断引起的行为缺陷与之前在 STN 神经毒性损伤后观察到的行为缺陷相似，表明该结构中的 NMDA 受体作为 STN 的功能输出发挥着重要作用。此外，考虑到相同剂量的 APV 在 SNr 和 EP 中产生的差异效应，这两个传统上认为在功能上相关的结构不应被视为基底神经节流出组织中的同一功能实体。
Overactivity of the excitatory amino acid outputs of the subthalamic nucleus (STN) has recently been found to be one of the cascade of subsequent disruptions caused by nigrostriatal dopaminergic degeneration in Parkinson's disease. The respective contribution of the excitatory glutamatergic output structures of the STN [i.e. the globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr)] to the control of movement is not known, however. To investigate further the function of glutamatergic transmission through NMDA receptor subtypes in these three structures, the effects of discrete local infusion of a competitive receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV), into the EP, GP and SNr were tested in rats performing a reaction time task. Bilateral infusion of APV into the different output structures of the STN differentially impaired the performance of rats trained to release a lever after the onset of a visual stimulus within a time limit to obtain a food reward. Infusion of APV (0.25 and 0.5 mu g/0.5 mu l) into the SNr was found to induce behavioural deficits characterized by a dramatic increase in the number of premature lever releases and decreased mean reaction time. In contrast, the infusion of APV at a dose of 0.25 mu g into the GP or EP was found to induce a motor initiation deficit characterized by an increased number of delayed responses (lever release after the time limit) and increased mean reaction time. At a dose of 0.5 mu g, a premature responding deficit was added to the previous motor impairment. Interestingly, when APV was infused simultaneously into the GP and SNr in the same animals, the behavioural effects tended to be similar to those observed after a single infusion into the SNr. Altogether, these results reveal that the different functional weight of the three main output pathways originating at the STN level is t.o. The behavioural deficits induced by NMDA receptor blockade in the SNr were similar to those observed previously after a neurotoxic lesion of the STN, suggesting that NMDA receptors in this structure play a major role as a functional output of the STN. Furthermore, regarding the differential effects produced by the same dose of APV in the SNr and the EP, these two structures, which are classically believed to be functionally linked should not be considered as the same functional entity in the organization of basal ganglia outflow.