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Axonal arborization of dopaminergic neurons of the rat midbrain:mechanism of Parkinson's disease

大鼠中脑多巴胺能神经元的轴突树枝化：帕金森病的机制

基本信息

批准号：
22500307
负责人：
MATSUDA Wakoto
金额：
$ 2.75万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2012
项目状态：
已结题

项目摘要

The axonal arbors of nigrostriatal dopaminergicneurons were visualized with a viral vector expressing membrane-targeted green fluorescent protein in rat brain. As results, all eight reconstructed tyrosine hydoroxylase-positive dopaminergic neurons possessed widely spread and highly dense axonal arborizations in the neostriatum. The striatal axonal bush of each reconstructed dopaminergic neurons covered 0.45 - 5.7% (mean ± S.D. = 2.7 ± 1.5%) of the total volume of the neostriatum. Furthermore, all the dopaminergic neurons innervated both striosome and matrix compartments of the neostriatum, although each neuron's arborization tended to favor one of these compartments. Detail morphological images of DA neurons derived from this new approach are used to elucidate the role of DA neurons in PD. Firstly, we point out how the new images reveal how DA neurons have a massive axonal arborization in the striatum. This arborization is on a scale not previously known, and of a form that implies both a particular vulnerability and a redundancy in DA neurons. Secondly, we describe how the imaging results indicate that DA neurons innervate both the striosome and the matrix compartments of the striatum. This dual innervation has implications for reinforcement learning in the basal ganglia,with further implications for how normal behavior is driven and how it may be disrupted by Levodopa PD therapies. In conclusion, these results would also contribute to understanding the clinicopathology of Parkinson's disease and related syndromes

用表达膜靶向绿色荧光蛋白的病毒载体在大鼠脑内观察黑质纹状体多巴胺能神经元的轴突主干。结果表明，所有8个重建的酪氨酸羟化酶阳性多巴胺能神经元在新纹状体中具有广泛分布和高度密集的轴突分支。每个重建的多巴胺能神经元的纹状体轴突丛覆盖0.45 - 5.7%（平均值± SD = 2.7 ± 1.5%）。此外，所有的多巴胺能神经元支配的纹状体和基质车厢的新纹状体，虽然每个神经元的树枝状倾向于有利于这些车厢之一。详细的形态学图像的DA神经元来自这种新的方法被用来阐明DA神经元在PD中的作用。首先，我们指出新的图像如何揭示DA神经元在纹状体中有大量的轴突分支。这种树枝状化的规模是以前所不知道的，并且其形式意味着DA神经元中的特定脆弱性和冗余性。其次，我们描述了如何成像结果表明，DA神经元支配的纹状体和纹状体的基质车厢。这种双重神经支配对基底神经节中的强化学习有影响，进一步影响了正常行为是如何驱动的，以及左旋多巴PD治疗如何破坏正常行为。总之，这些结果也将有助于了解帕金森病和相关综合征的临床病理学