EARLY DEVELOPMENT OF OLIVOCEREBELLAR PROJECTIONS IN THE FETAL-RAT USING CGRP IMMUNOCYTOCHEMISTRY
EARLY DEVELOPMENT OF OLIVOCEREBELLAR PROJECTIONS IN THE FETAL-RAT USING CGRP IMMUNOCYTOCHEMISTRY
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DOI：
10.1111/j.1460-9568.1992.tb00142.x
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发表时间：
1992-11-01
影响因子：
3.4
通讯作者：
SOTELO, C
中科院分区：
文献类型：
--
作者：
CHEDOTAL, A;SOTELO, C
降钙素基因相关肽（CGRP）免疫反应性在某些下橄榄神经元的表达是短暂的和发育调节。标记的神经元开始出现在胚胎第16天（E16），并在出生后第2天（P2）达到最大程度。标记的消失发生在P13和P16之间。CGRP免疫反应性的表达也观察到在一些小脑纤维从E17，当轴突在网状束开始进入内侧小脑实质。它们的最大程度在P6达到，此后它们按照精确的模式慢慢消失，尽管纤维灭绝不完全。橄榄分布的标记神经元和小脑标记纤维的变化的时空变化遵循已知的模式的地形安排的橄榄小脑系统在成年大鼠。此外，CGRP标记的纤维在出生后大鼠的发育阶段对应于那些已知的攀爬纤维表型收购。因此，CGRP免疫细胞化学鉴定在胎鼠的一个子集的下橄榄神经元和它们相应的小脑攀爬纤维。使用这种方法，我们分析了一些最初的事件导致橄榄小脑投射的形成，并获得了以下信息：（i）橄榄小脑轴突不是随机分布在网状束之前，他们进入小脑。(ii)在小脑板的喙侧半表面存在大量选择时，标记的橄榄轴突开始在精确的中间点进入小脑，邻接仅由迁移的浦肯野细胞组成的区域，并在这些神经元到达其最终皮质位置之前与其靶细胞建立联系。(iii)从E18到E19，标记的纤维束失去其表面位置，被迁移的浦肯野细胞绕过，占据与预期的白色物质相对应的区域。这种易位与第二个轴突进入点的发生是一致的，比前一个更侧向，并出现了一个新的标记纤维的横向条纹。(iv)早期和晚期出现的标记条纹从它们形成的时候起就一直局限在精确的小脑区域，这表明只有一些浦肯野细胞簇与CGRP纤维接触。所获得的结果意味着，既没有一个等待期，也没有一个初始阶段的随机性形成的橄榄小脑投影地图。这种混乱的小脑入侵的缺乏以及入口点的高选择性表明，CGRP阳性橄榄小脑纤维朝向其目标的方向是由橄榄神经元子集和浦肯野细胞簇之间共享的位置信息调节的。这一过程的结果将是形成早熟的粗糙形貌，需要进一步细化。
The expression of calcitonin gene-related peptide (CGRP) immunoreactivity in certain inferior olivary neurons is transient and developmentally regulated. Labelled neurons begin to appear at embryonic day 16 (E16), and reach their maximal extent by postnatal day 2 (P2). The extinction of the labelling occurs between P13 and P16. Expression of CGRP immunoreactivity is also observed in a few cerebellar fibres from E17, when axons in the restiform bundle begin to enter medially the cerebellar parenchyma. Their maximal extent is reached by P6, and thereafter they slowly disappear following a precise pattern, although fibre extinction is not complete. The spatio-temporal changes in the olivary distribution of the labelled neurons and the changes in the cerebellar labelled fibres follow the known pattern of topographic arrangement of the olivocerebellar system in adult rats. Moreover, the developmental phases of the CGRP-labelled fibres in postnatal rats correspond to those known for climbing fibre phenotypic acquisition. Thus, CGRP immunocytochemistry identifies in the fetal rat a subset of inferior olivary neurons and their corresponding cerebellar climbing fibres. Using this approach, we have analysed some of the initial events leading to the formation of the olivocerebellar projection, and obtained the following information: (i) Olivocerebellar axons are not randomly distributed in the restiform bundle before they enter the cerebellum. (ii) In the presence of a large spectrum of choices at the surface of the rostral half of the cerebellar plate the labelled olivary axons begin to enter the cerebellum at a precise medial point to abut a region composed solely of migrating Purkinje cells, and establish contacts with their targets before these neurons reach their final cortical location. (iii) From E18 to E19, the bundle of labelled fibres loses its superficial location, being bypassed by migrating Purkinje cells, to occupy a region corresponding to the prospective white matter. This translocation is coincident with the occurrence of a second axonal entry point, somewhat more lateral than the previous one, and with the appearance of a new lateral stripe of labelled fibres. (iv) Both the early and the late appearing labelled stripes remain confined from the time of their formation in precise cerebellar territories, indicating that only some clusters of Purkinje cells are contacted by the CGRP fibres. The results obtained imply that there is neither a waiting period nor an initial phase of randomness in the formation of the olivocerebellar projection map. This absence of chaotic cerebellar invasion, and the high selectivity of the entry points, suggest that the orientation of CGRP-positive olivocerebellar fibres towards their targets is regulated by positional information shared between subsets of olivary neurons and clusters of Purkinje cells. The result of this process would be the formation of a precocious coarse topography that would need further refinement.