Implications of activity dependent neurite outgrowth for neuronal morphology and network development.
Implications of activity dependent neurite outgrowth for neuronal morphology and network development.
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活动依赖性神经突生长对神经元形态和网络发育的影响。
DOI：
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发表时间：
1995
影响因子：
2
通讯作者：
M. Corner
中科院分区：
文献类型：
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作者：
A. van Ooyen;J. van Pelt;M. Corner
实证研究表明，神经元的电活动可以直接影响神经突的生长。在本文中，我们使用最初断开连接的细胞在其内在活动的影响下将自身组织成网络的模型，研究活动依赖性神经突生长对神经元形态和网络发育的可能影响。神经元被建模为神经炎场，其生长取决于其自身的活动水平，当神经元的场重叠时，神经元就会相互连接。在纯粹的兴奋性网络中，我们之前已经证明，活动依赖性的生长与具有某种形式的放电阈值的神经元反应函数相结合，足以导致连接或突触数量的短暂过量（超调）。在这里，我们表明，过度调节仍然发生在兴奋性和抑制性细胞网络中，甚至可以增强。随着抑制发展的延迟，抑制连接数量的增长曲线不再表现出超调。该模型的一个有趣的新特性是，仅作为简单的生长规则和细胞相互作用的结果，抑制性细胞的（树突）区域往往会变得小于兴奋性细胞的区域，即使两种类型的细胞具有相同的生长特性。生长、兴奋和抑制之间相互作用的其他后果是：（i）抑制细胞的空间分布对于确定抑制水平变得重要； (ii) 如果网络在没有适当电气活动的情况下增长超过某个关键时期，则无法再进行连接修剪； (iii) 抑制细胞通过诱导生长，可以帮助连接结构的不同部分。此外，该模型预测兴奋性细胞死亡将伴随着存活神经元的神经炎区的增加（“补偿性出芽”）。该模型与离解细胞组织培养物的发现的相似性得到了广泛讨论。
Empirical studies have demonstrated that electrical activity of the neuron can directly affect neurite outgrowth. In this paper, we study the possible implications of activity-dependent neurite outgrowth for neuronal morphology and network development, using a model in which initially disconnected cells organize themselves into a network under the influence of their intrinsic activity. A neuron is modelled as a neuritic field, the growth of which depends on its own level of activity, and neurons become connected when their fields overlap. In a purely excitatory network, we have previously demonstrated that activity-dependent outgrowth in combination with a neuronal response function with some form of firing threshold is sufficient to cause a transient overproduction (overshoot) in the number of connections or synapses. Here we show that overshoot still takes place in a network of excitatory and inhibitory cells, and can even be enhanced. With delayed development of inhibition the growth curve of the number of inhibitory connections no longer exhibits overshoot. An interesting emergent property of the model is that, solely as the result of simple outgrowth rules and cell interactions, the (dendritic) fields of the inhibitory cells tend to become smaller than those of the excitatory cells, even if both type of cells have the same outgrowth properties. Other consequences of the interactions among outgrowth, excitation and inhibition are that (i) the spatial distribution of inhibitory cells becomes important in determining the level of inhibition; (ii) pruning of connections can no longer take place if the network has grown without proper electrical activity for longer than a certain critical period; (iii) inhibitory cells, by inducing outgrowth, can help to connect different parts of a structure. Further, the model predicts that excitatory cell death will be accompanied by an increased neuritic field of surviving neurons ("compensatory sprouting"). The similarities of the model with findings in developing tissue cultures of dissociated cells are extensively discussed.