Andjus P R, Zhu L, Cesa R, Carulli D, Strata P
Rita Levi Montalcini Center for Brain Repair, Department of Neuroscience, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.
Neuroscience. 2003;121(3):563-72. doi: 10.1016/s0306-4522(03)00556-6.
Pattern of activity during development is important for the refinement of the final architecture of the brain. In the cerebellar cortex, the regression from multiple to single climbing fiber innervation of the Purkinje cell occurs during development between postnatal days (P) 5 and 15. However, the regression is hampered by altering in various ways the morpho-functional integrity of the parallel fiber input. In rats we disrupted the normal activity pattern of the climbing fiber, the terminal arbor of the inferior olive neurons, by administering harmaline for 4 days from P9 to P12. At all studied ages (P15-87) after harmaline treatment multiple (double only) climbing fiber EPSC-steps persist in 28% of cells as compared with none in the control. The ratio between the amplitudes of the larger and the smaller climbing fiber-evoked EPSC increases in parallel with the decline of the polyinnervation factor, indicating a gradual enlargement of the synaptic contribution of the winning climbing fiber synapse at the expense of the losing one. Harmaline treatment had no later effects on the climbing fiber EPSC kinetics and I/V relation in Purkinje cells (P15-36). However, there was a rise in the paired-pulse depression indicating a potentiation of the presynaptic mechanisms. In the same period, after harmaline treatment, parallel fiber-Purkinje cell electrophysiology was unaffected. The distribution of parallel fiber synaptic boutons was also not changed. Thus, a change in the pattern of activity during a narrow developmental period may affect climbing fiber-Purkinje cell synapse competition resulting in occurrence of multiple innervation at least up to 3 months of age. Our results extend the current view on the role of the pattern of activity in the refinement of neuronal connections during development. They suggest that many similar results obtained by different gene or receptor manipulations might be simply the consequence of disrupting the pattern of activity.
发育过程中的活动模式对于大脑最终结构的完善至关重要。在小脑皮质中，浦肯野细胞从多条攀缘纤维支配向单条攀缘纤维支配的回归发生在出生后第（P）5天至15天的发育期间。然而，通过以各种方式改变平行纤维输入的形态功能完整性，这种回归会受到阻碍。在大鼠中，我们从P9至P12连续4天给予哈马灵，从而破坏了攀缘纤维（下橄榄核神经元的终末分支）的正常活动模式。在哈马灵处理后的所有研究年龄（P15 - 87），28%的细胞中存在多条（仅为两条）攀缘纤维EPSC阶梯，而对照组中则没有。较大和较小的攀缘纤维诱发的EPSC幅度之比随着多神经支配因子的下降而平行增加，这表明获胜的攀缘纤维突触的突触贡献逐渐增大，而以失败的突触为代价。哈马灵处理对浦肯野细胞（P15 - 36）的攀缘纤维EPSC动力学和I/V关系没有后期影响。然而，双脉冲抑制有所增加，表明突触前机制增强。在同一时期，哈马灵处理后，平行纤维 - 浦肯野细胞的电生理未受影响。平行纤维突触小体的分布也没有改变。因此，在狭窄的发育时期活动模式的改变可能会影响攀缘纤维 - 浦肯野细胞突触竞争，导致至少在3个月龄之前出现多神经支配。我们的结果扩展了当前关于活动模式在发育过程中神经元连接完善作用的观点。它们表明，通过不同基因或受体操作获得的许多类似结果可能仅仅是破坏活动模式的结果。
