A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth
A Multi-Component Model of the Developing Retinocollicular Pathway Incorporating Axonal and Synaptic Growth
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DOI：
10.1371/journal.pcbi.1000600
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发表时间：
2009-12-01
影响因子：
4.3
通讯作者：
Swindale, Nicholas V.
中科院分区：
文献类型：
--
作者：
Godfrey, Keith B.;Eglen, Stephen J.;Swindale, Nicholas V.
在发育过程中，神经元将轴突延伸到不同的大脑区域并产生典型的连接模式。这一过程背后的机制已在视觉系统中得到深入研究，其中视网膜神经元在丘脑和上丘中形成视网膜专题图。地图形成中的活跃机制包括分子引导线索、营养因子释放、自发神经活动、尖峰时间依赖性可塑性 (STDP)、突触产生和回缩以及轴突生长、分支和回缩。为了研究这些机制如何相互作用，基于每种机制的现象学近似，建立了发育中的视网膜小球通路的多组分模型。该模型的核心假设是，当化学亲和力和营养因子线索的综合影响最高时，轴突分支和突触生长的概率最高，并且营养因子的活动依赖性释放起到稳定突触的作用。基于这些行为，模型轴突产生形态上真实的生长模式，并投射到丘中视网膜局部的正确位置。该模型的发现包括 STDP、轴突生长锥的梯度检测和丘脑神经元之间的横向连接对于细化来说不是必需的，并且轴突生长的指导性线索似乎首先由分子引导介导，然后由神经活动介导。尽管很复杂，但该模型似乎对组件开发机制实现方式的变化不敏感。轴突和突触的活动、分子引导以及生长和缩回是神经发育的常见特征，这项研究的结果可能与视网膜小球通路组织之外的相关。
During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multicomponent model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway.