Ramakers G J, Winter J, Hoogland T M, Lequin M B, van Hulten P, van Pelt J, Pool C W
Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam, Netherlands.
Brain Res Dev Brain Res. 1998 Jun 15;108(1-2):205-16. doi: 10.1016/s0165-3806(98)00050-9.
Electric activity is known to have profound effects on growth cone morphology and neurite outgrowth, but the nature of the response varies strongly between neurons derived from different species or brain areas. To establish the role of electric activity in neurite outgrowth and neuronal morphogenesis of rat cerebral cortex neurons, cultured neurons were depolarized for up to 72 h and quantitatively analyzed for changes in axonal and dendritic morphology. Depolarization with 25 mM potassium chloride induced a rapid increase in lamellipodia in almost all growth cones and along both axons and dendrites. Lamellipodia formation was dependent on an influx of extracellular calcium through L-type voltage-sensitive calcium channels. Prolonged depolarization for 24 h induced an increase in total axonal length, mainly due to an increase in branching. After three days of depolarization axonal outgrowth was largely the same as in control neurons, suggesting accommodation of the growth cones to chronic depolarization. Dendrites showed very little change during the first three days in culture, and dendritic length or branching were not affected by depolarization. Thus, in early cerebral cortex neurons depolarization specifically stimulates axonal outgrowth through increased branching. This increase in branching may be a consequence of the earlier increase in lamellipodia formation. In contrast, early dendrites seem to be unable to translate the increase in lamellipodia into changes in outgrowth or branching. This difference between axons and dendrites could be due to differences in the stabilization of the tubulin cytoskeleton.
已知电活动对生长锥形态和神经突生长有深远影响，但不同物种或脑区来源的神经元，其反应性质差异很大。为确定电活动在大鼠大脑皮层神经元神经突生长和神经元形态发生中的作用，对培养的神经元进行长达72小时的去极化处理，并对轴突和树突形态的变化进行定量分析。用25 mM氯化钾进行去极化处理，几乎所有生长锥以及轴突和树突上的片状伪足都迅速增加。片状伪足的形成依赖于细胞外钙通过L型电压敏感钙通道的内流。持续去极化24小时会导致轴突总长度增加，主要是由于分支增加。去极化三天后，轴突生长与对照神经元基本相同，表明生长锥对慢性去极化产生了适应。在培养的前三天，树突变化很小，去极化不影响树突长度或分支。因此，在早期大脑皮层神经元中，去极化通过增加分支特异性地刺激轴突生长。分支增加可能是早期片状伪足形成增加的结果。相比之下，早期树突似乎无法将片状伪足的增加转化为生长或分支的变化。轴突和树突之间的这种差异可能是由于微管蛋白细胞骨架稳定性的差异。
