A change in the pattern of activity affects the developmental regression of the purkinje cell polyinnervation by climbing fibers in the rat cerebellum

A change in the pattern of activity affects the developmental regression of the purkinje cell polyinnervation by climbing fibers in the rat cerebellum
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DOI:
10.1016/s0306-4522(03)00556-6
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发表时间:
2003-01-01
期刊:
影响因子:
3.3
通讯作者:
Strata, P
Strata, P
中科院分区:
医学3区
文献类型:
--
作者:
Andjus, PR;Zhu, L;Strata, P

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发育过程中的活动模式对于大脑最终结构的完善是很重要的。在小脑皮层,浦肯野细胞从多攀爬纤维神经支配向单攀爬纤维神经支配的退化发生在出生后5 ~ 15天。然而,由于以各种方式改变平行纤维输入的形态功能完整性,这种回归受到阻碍。在大鼠中,我们通过从P9到P12给药4天,破坏了下橄榄神经元末端乔木攀爬纤维的正常活动模式。在所有研究年龄(P15-87岁),经丙烯碱处理后,28%的细胞持续存在多个(仅两倍)攀爬纤维epsc步骤,而对照组则没有。较大和较小的攀爬纤维诱发EPSC的振幅之比与多神经支配因子的下降平行增加,表明获胜的攀爬纤维突触的突触贡献逐渐增加,而失败的攀爬纤维突触的贡献则逐渐减少。Harmaline处理对浦肯野细胞攀爬纤维EPSC动力学和I/V关系无后期影响(P15-36)。然而,配对脉冲抑制的增加表明突触前机制的增强。在同一时期,经正碱处理后,平行纤维-浦肯野细胞电生理未受影响。平行纤维突触钮扣的分布也没有改变。因此,在一个狭窄的发育时期,活动模式的变化可能会影响攀爬纤维-浦肯野细胞突触的竞争,导致至少3个月大的多神经支配的发生。我们的结果扩展了目前关于活动模式在发育过程中神经元连接改进中的作用的观点。他们认为,通过不同的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。(c) 2003年。Elsevier Ltd.出版。版权所有。
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. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved.