Sugihara Izumi, Lohof Ann M, Letellier Mathieu, Mariani Jean, Sherrard Rachel M
Department of Systems Neurophysiology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
Eur J Neurosci. 2003 Dec;18(11):3027-36. doi: 10.1111/j.1460-9568.2003.03045.x.
In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon-target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch-clamp PC recording of CF-induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo-cortico-nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions.
在成年哺乳动物的中枢神经系统中，创伤后的神经再支配和恢复是有限的。然而，在发育过程中，损伤后的可塑性可能会产生替代路径，为研究再支配轴突与靶标的相互作用提供模型。新生大鼠橄榄小脑通路单侧横断后，同侧下橄榄核的轴突生长到失神经支配的小脑半球，并在浦肯野细胞（PC）上形成类似攀缘纤维（CF）的分支。然而，PC再支配的突触功能和程度仍然未知。在出生后第3天进行脑桥切断术的成年大鼠中，利用轴突重建和CF诱导的突触电流的膜片钳PC记录，研究了再支配橄榄小脑轴突的形态和电生理特性。再支配的PC显示出正常的CF电流，并且PC再支配的频率随着偏侧性增加而降低。再支配的CF分支主要是正常的，但有6%在分子层内分支形成较小的二级分支。CF起源于经连合的橄榄轴突，这些轴突在其靶标PC附近广泛分支，平均产生36个CF，是正常情况的6倍。终止于半球的轴突比终止于蚓部的轴突形成更多的CF。然而，精确的矢状旁微区组织得以保留。经连合轴突也会分支，尽管程度较小，延伸至小脑深部核团，并以一种表明橄榄-皮质-核回路的分布终止。这些结果表明，再支配橄榄小脑的轴突在小脑中具有高度可塑性，在解剖学和功能上补偿出生后早期的失神经支配，并且这种修复遵循精确的地形学限制，尽管轴突可塑性会受到靶标（PC或深部核神经元）相互作用的影响。
