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

用表达膜靶向绿色荧光蛋白的病毒载体在大鼠脑内显示黑质纹状体多巴胺能神经元的轴突。结果显示，所有8个重建的酪氨酸羟氧基酶阳性的多巴胺能神经元在新纹状体内均有广泛分布和高度致密的轴突分支。每个重建的多巴胺能神经元的纹状体轴索占新纹状体总体积的0.45~5.7%(平均值±SD=2.7±1.5%)。此外，所有的多巴胺能神经元都支配新纹状体的纹状体和基质隔室，尽管每个神经元的树枝倾向于其中一个隔室。从这一新方法获得的DA神经元的详细形态图像被用来阐明DA神经元在帕金森病中的作用。首先，我们指出了新的图像如何揭示了DA神经元如何在纹状体有大量的轴突树枝。这种分支的规模是以前未知的，其形式暗示着DA神经元中的特定脆弱性和冗余。其次，我们描述了成像结果如何表明DA神经元既支配纹状体的纹状体又支配纹状体的基质隔室。这种双重神经支配对基底神经节的强化学习有影响，对正常行为是如何驱动的，以及左旋多巴PD疗法可能如何扰乱正常行为有进一步的影响。总之，这些结果也将有助于理解帕金森病和相关综合征的临床病理

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