Hely T A, Graham B, Ooyen A V
Division of Informatics, Institute for Adaptive and Neural Computation, University of Edinburgh, 5 Forrest Hill, Edinburgh, Scotland, EH1 2QL, UK.
J Theor Biol. 2001 Jun 7;210(3):375-84. doi: 10.1006/jtbi.2001.2314.
We introduce a new computational model of dendritic development in neurons. In contrast to previous models, our model explicitly includes cellular mechanisms involved in dendritic development. It is based on recent experimental data which indicates that the phosphorylation state of microtubule-associated protein 2 (MAP2) may play a key role in controlling dendritic elongation and branching (Audesirk et al., 1997). Dephosphorylated MAP2 favours elongation by promoting microtubule polymerization and bundling, whilst branching is more likely to occur when MAP2 is phosphorylated and microtubules are spaced apart. In the model, the rate of elongation and branching is directly determined by the ratio of phosphorylated to dephosphorylated MAP2. This is regulated by calmodulin-dependent protein kinase II (CaMKII) and calcineurin, which are both dependent on the intracellular calcium concentration. Results from computer simulations of the model suggest that the wide variety of branching patterns observed among different cell types may be generated by the same underlying mechanisms and that elongation and branching are not necessarily independent processes. The model predicts how the branching pattern will change following manipulations with calcium, CaMKII and MAP2 phosphorylation.
我们介绍了一种神经元树突发育的新计算模型。与之前的模型不同，我们的模型明确纳入了参与树突发育的细胞机制。它基于最近的实验数据，这些数据表明微管相关蛋白2（MAP2）的磷酸化状态可能在控制树突伸长和分支中起关键作用（奥德斯克等人，1997年）。去磷酸化的MAP2通过促进微管聚合和捆绑来促进伸长，而当MAP2磷酸化且微管间距增大时更可能发生分支。在该模型中，伸长和分支的速率直接由磷酸化MAP2与去磷酸化MAP2的比例决定。这由钙调蛋白依赖性蛋白激酶II（CaMKII）和钙调神经磷酸酶调节，二者均依赖于细胞内钙浓度。该模型的计算机模拟结果表明，不同细胞类型中观察到的多种分支模式可能由相同的潜在机制产生，并且伸长和分支不一定是独立的过程。该模型预测了在对钙、CaMKII和MAP2磷酸化进行操作后分支模式将如何变化。
