Marty S, Weinitz J M, Peschanski M
INSERM CJF 91-02, Faculté de médecine, Créteil, France.
J Neurosci. 1994 Sep;14(9):5257-66. doi: 10.1523/JNEUROSCI.14-09-05257.1994.
During development, the survival of neurons in the CNS depends critically on interactions with postsynaptic target cells. The role of target cells on the maintenance of afferent neurons in the adult, however, is a matter of controversy. Morphological alterations of target-deprived neurons, such as axonal retraction or pruning, may occur. We have therefore undertaken an analysis of target-deprived neurons over time after an excitotoxic lesion in order to investigate these potential changes. Dorsal column nuclei (DCN) neurons were deprived of their target neurons in adult rats by the injection of kainic acid into the ventrobasal thalamic complex. Anterogradely transported wheat germ agglutinin conjugated to HRP from the DCN showed a progressive decrease of the density of afferent terminals during the first month after lesion. Density stabilized thereafter through the longest time studied (8 months). In contrast, the extent of the area occupied by DCN projections did not change up to 1 month and then shrank over time. These results indicated a continuous decrease in the number of axonal elements in the lesion, which is the strongest during the first month postlesion. To interpret these data, we then studied axonal morphology. Diffusion-filled lemniscal axons were labeled by WGA-HRP injections aimed at the medial lemniscus. There was no conspicuous alteration of axonal stems in the medial lemniscus. Terminal axonal arborizations and swellings dramatically decreased in number over the first month after the kainate injection, and large axonal varicosities were formed over the same period of time. These morphological data suggest that the decrease in number of axons in an excitotoxic lesion is related, at least during the first month, to a loss of axonal terminal arborizations rather than to a retraction of axonal stems. The pattern of terminal arborizations in the adult CNS may therefore depend critically on interactions of afferents with their target neurons, while the maintenance of the axonal stems does not.
在发育过程中，中枢神经系统（CNS）中神经元的存活严重依赖于与突触后靶细胞的相互作用。然而，靶细胞在成体中对传入神经元维持的作用仍存在争议。靶细胞缺失的神经元可能会出现形态学改变，如轴突回缩或修剪。因此，为了研究这些潜在变化，我们对兴奋性毒性损伤后的靶细胞缺失神经元进行了长期分析。通过向成年大鼠腹侧基底丘脑复合体注射 kainic 酸，使背柱核（DCN）神经元的靶神经元缺失。从 DCN 逆行运输的与 HRP 结合的小麦胚凝集素显示，损伤后的第一个月内传入终末的密度逐渐降低。此后，在所研究的最长时间（8 个月）内密度保持稳定。相比之下，DCN 投射所占据区域的范围在 1 个月内没有变化，然后随时间逐渐缩小。这些结果表明损伤部位轴突成分的数量持续减少，在损伤后的第一个月最为明显。为了解释这些数据，我们随后研究了轴突形态。通过向内侧丘系注射 WGA-HRP 标记充满扩散的薄束轴突。内侧丘系的轴突干没有明显改变。在注射 kainate 后的第一个月内，终末轴突分支和肿胀的数量显著减少，同时在同一时期形成了大的轴突膨体。这些形态学数据表明，兴奋性毒性损伤中轴突数量的减少，至少在第一个月，与轴突终末分支的丧失有关，而不是轴突干的回缩。因此，成年中枢神经系统中终末分支的模式可能严重依赖于传入神经元与其靶神经元的相互作用，而轴突干的维持则不然。
