Rossi F, Wiklund L, van der Want J J, Strata P
Department of Human Anatomy and Physiology, University of Turin, Italy.
J Comp Neurol. 1991 Jun 22;308(4):513-35. doi: 10.1002/cne.903080403.
Cerebellar climbing fibres react by collateral sprouting after subtotal lesions of the inferior olive, and the newly formed branches are able to reinnervate neighbouring denervated Purkinje cells. In the present paper, we used the Phaseolus vulgaris leucoagglutinin (PHA-L) tracing technique to label the climbing fibres and study their plasticity in detail at the light microscopical level. The specific objectives were to study the time course and morphological aspects of their sprouting, to estimate their extent of growth, and to compare the newly formed terminal plexuses with normal climbing fibres. Intraperitoneal injection of 3-acetylpyridine induced degeneration of the majority of the olivary neurones, which terminate as climbing fibres in the cerebellar cortex. Regularly, small numbers of neurones survived in the inferior olive. In the cerebellar cortex scattered surviving climbing fibres were found, which were devoid of any sign of injury. Already 3 days after the lesion, surviving climbing fibres had emitted collateral branches, which elongated for some distance through the molecular layer and ended with a number of varicosities and very fine branchlets. By 7 days, it was possible to recognize new developing arbours which grew in the molecular layer with the same orientation as normal climbing fibres. At longer survival times, extensive terminal arbours had developed and double labelling experiments confirmed that they terminated around the proximal dendrites of Purkinje cells. The newly formed terminal plexuses resembled, in all essential aspects, normal climbing fibres. In addition, from 1 month onward, it was evident that every surviving climbing fibre was able to form several new terminal plexuses reinnervating a number of neighbouring Purkinje cells. The result of this process was the formation of large clusters of newly formed plexuses around the parental arborization. Quantitative estimates indicated that the domain of innervation of single surviving climbing fibres could be increased by more than six times. It is concluded that climbing fibres surviving a subtotal olivary lesion are capable of extensive sprouting, axonal growth, and formation of new terminal plexuses, which resemble normal climbing fibres. Previous electrophysiological evidence indicates that this reinnervation is functional. The high specificity with which sprouting olivary axons reinnervate the proximal Purkinje cell dendrites suggests the existence of precise interactions between the growing fibres and their target. This example of "homotypic" collateral sprouting and reinnervation may thus provide a useful model for the study of nerve-target interactions.
在下橄榄体次全损伤后，小脑攀缘纤维通过侧支发芽做出反应，新形成的分支能够重新支配相邻的去神经支配的浦肯野细胞。在本文中，我们使用菜豆白细胞凝集素（PHA-L）追踪技术标记攀缘纤维，并在光学显微镜水平详细研究其可塑性。具体目标是研究其发芽的时间进程和形态学方面，估计其生长范围，并将新形成的终末丛与正常攀缘纤维进行比较。腹腔注射3-乙酰吡啶可导致大多数橄榄神经元变性，这些神经元以攀缘纤维的形式终止于小脑皮质。通常，少量神经元在下橄榄体中存活。在小脑皮质中发现了散在的存活攀缘纤维，它们没有任何损伤迹象。损伤后3天，存活的攀缘纤维就发出了侧支，这些侧支在分子层中延伸了一段距离，末端有许多曲张和非常细的小分支。到7天时，可以识别出新形成的、在分子层中与正常攀缘纤维具有相同取向生长的树突。在更长的存活时间里，广泛的终末树突已经形成，双重标记实验证实它们终止于浦肯野细胞近端树突周围。新形成的终末丛在所有基本方面都类似于正常攀缘纤维。此外，从1个月起，很明显每个存活的攀缘纤维都能够形成几个新的终末丛，重新支配一些相邻的浦肯野细胞。这个过程的结果是在亲代树突周围形成了大量新形成的丛簇。定量估计表明，单个存活攀缘纤维的支配区域可以增加六倍以上。结论是，在下橄榄体次全损伤后存活的攀缘纤维能够进行广泛的发芽、轴突生长和形成类似于正常攀缘纤维的新终末丛。先前的电生理证据表明这种重新支配是有功能的。发芽的橄榄轴突对浦肯野细胞近端树突进行重新支配的高度特异性表明生长纤维与其靶标之间存在精确的相互作用。因此，这种“同型”侧支发芽和重新支配的例子可能为研究神经-靶标相互作用提供一个有用的模型。
