The regulatory connection between the activity of granule cell NMDA receptors and dendritic differentiation of cerebellar Purkinje cells
The regulatory connection between the activity of granule cell NMDA receptors and dendritic differentiation of cerebellar Purkinje cells
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DOI：
10.1523/jneurosci.20-14-05217.2000
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发表时间：
2000-07-15
影响因子：
5.3
通讯作者：
Launey, T
中科院分区：
文献类型：
--
作者：
Hirai, H;Launey, T
已知小脑颗粒细胞是浦肯野细胞分化的强大诱导剂。但该规定的具体机制尚未明确。在这里，利用小脑神经元培养，我们发现颗粒细胞表达的 NMDA 受体的激活触发了浦肯野细胞树突分化的信号通路。该信号已被证明可以通过 BDNF 介导的 TrkB 激活促进颗粒细胞存活，通过增加颗粒-浦肯野细胞相互作用导致浦肯野细胞分化。在颗粒细胞向浦肯野细胞树突提供的可能信号分子中，一氧化氮被发现对树突生长和分支没有影响，但电活动和随后的细胞内Ca2+增加被认为在树突的分支和增厚中发挥重要作用，因为非NMDA和代谢型谷氨酸受体的阻断导致分支点数量和浦肯野直径显着减少树突，而不会明显影响树突延伸和脊柱形成。总的来说，这些结果表明浦肯野细胞分化受到两个连续步骤的调节。第一步是由颗粒细胞中 NMDA 受体介导的信号启动，该信号充当颗粒细胞的营养因子。第二步涉及激活颗粒-浦肯野突触，提供浦肯野细胞分化所必需的神经营养物质和电活动。
It is known that cerebellar granule cells are powerful inducers for the differentiation of Purkinje cells. However, the detailed mechanism of this regulation has not yet been clarified. Here, using cerebellar neuronal culture, we show that the activation of NMDA receptors expressed by granule cells triggers the signaling pathway for the dendritic differentiation of Purkinje cells. This signal has been shown to promote the granule cell survival through BDNF-mediated TrkB activation, leading to Purkinje cell differentiation by increasing the granule-Purkinje cell interaction. Among the possible signal molecules provided to the dendrites of Purkinje cells from granule cells, nitric oxide was found to have no effect on the dendritic outgrowth and branching, but electrical activity and the subsequent intracellular Ca2+ increase were thought to play an important role in the branching and thickening of the dendrites, because blockade of both non-NMDA and metabotropic glutamate receptors caused a significant decrease in the number of branch points and the diameter of Purkinje dendrites without apparently affecting the dendrite extension and spine formation. Collectively, these results suggest that Purkinje cell differentiation is regulated by two successive steps. The first step is initiated by the NMDA receptor-mediated signal in granule cells, which acts as a trophic factor for granule cells. The second step involves the activation of granule-Purkinje synapses, providing neurotrophic substances and electrical activity essential for Purkinje cell differentiation.