Unilateral lesion of the pedunculopontine nucleus induces hyperactivity in the subthalamic nucleus and substantia nigra in the rat
Unilateral lesion of the pedunculopontine nucleus induces hyperactivity in the subthalamic nucleus and substantia nigra in the rat
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DOI：
10.1111/j.1460-9568.2005.04402.x
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发表时间：
2005-11-01
影响因子：
3.4
通讯作者：
Schulz, JB
中科院分区：
文献类型：
--
作者：
Breit, S;Lessmann, L;Schulz, JB
最近的数据表明脚桥核（PPN）在帕金森病的病理生理学中的作用。虽然有解剖学证据表明PPN和基底神经节是紧密相连的，但这些连接的功能重要性知之甚少。在灵长类动物中，PPN的损伤可诱导运动不能，而在6-羟基多巴胺大鼠模型中，发现PPN过度活跃。由于黑质纹状体多巴胺耗竭和PPN损伤均能诱导运动不能和帕金森病，因此本研究旨在研究单侧鹅膏蕈氨酸损伤PPN和单侧6-羟基多巴胺损伤黑质网状部（SNc）后丘脑底核（ENA）和黑质网状部（SNr）神经元活动的变化。PPN损伤后，PPN神经元的放电频率从10.2 ± 6.2（平均值± SD）显著增加至14.6 ± 11.7峰/秒，SNc损伤后增加至18.6 ± 14.5峰/秒。在PPN损伤后，SNr的活性从19.6 +/- 10.5显著增加到28.7 +/- 13.4尖峰/秒，在SNc损伤后增加到23.5 +/- 10.8尖峰/秒。此外，PPN损伤减少自发放电的多巴胺能SNc细胞的数量，而对其放电率没有影响。我们的研究结果表明，PPN的损害导致的过度活动，SNr，类似于由SNc的损害引起的变化。此外，PPN损伤后观察到的SNc细胞活性降低可能是PPN和SNr活性变化的起源。
Recent data suggest a role for the pedunculopontine nucleus (PPN) in the pathophysiology of Parkinson's disease. Although there is anatomical evidence that the PPN and the basal ganglia are reciprocally connected, the functional importance of these connections is poorly understood. Lesioning of the PPN was shown to induce akinesia in primates, whereas in the 6-hydroxydopamine rat model the PPN was found to be hyperactive. As both nigrostriatal dopamine depletion and lesioning of the PPN were shown to induce akinesia and parkinsonism, the present study was performed in order to investigate the changes in neuronal activity of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) after unilateral ibotenic acid lesioning of the PPN and after unilateral 6-hydroxydopamine lesioning of the substantia nigra pars compacta (SNc). The firing rate of STN neurones significantly increased from 10.2 +/- 6.2 (mean +/- SD) to 14.6 +/- 11.7 spikes/s after lesion of the PPN and to 18.6 +/- 14.5 spikes/s after lesion of the SNc. The activity of the SNr significantly increased from 19.6 +/- 10.5 to 28.7 +/- 13.4 spikes/s after PPN lesioning and to 23.5 +/- 10.8 spikes/s after SNc lesioning. Furthermore, PPN lesion decreased the number of spontaneously firing dopaminergic SNc cells, while having no effect on their firing rate. The results of our study show that lesion of the PPN leads to hyperactivity of the STN and SNr, similar to the changes induced by lesion of the SNc. Moreover, the decreased activity of SNc cells observed after PPN lesion might be at the origin of activity changes in the STN and SNr.