A developmental approach to predicting neuronal connectivity from small biological datasets: a gradient-based neuron growth model.

A developmental approach to predicting neuronal connectivity from small biological datasets: a gradient-based neuron growth model.
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DOI:
10.1371/journal.pone.0089461
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Soffe SR
Soffe SR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Borisyuk R;Al Azad AK;Conte D;Roberts A;Soffe SR

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神经回路的结构与功能关系是一个具有挑战性的问题。它需要证明脉冲活动的动态模式如何导致认知行为等功能,并识别导致回路适当活动的神经元和连接。我们采用“发育方法”来定义简单神经系统的连接组,其中神经元之间的连接不是规定的,而是作为神经元生长的结果出现的。本文建立了一种基于梯度的二维轴突生长的数学模型,该模型是由未分化的神经元行组成的,适用于爪蟾幼小蝌蚪脑干和脊髓中不同类型的神经元。模型参数定义了具有三种梯度信号的二维CNS生长环境,以及每种神经元类型的轴突对这些信号的特定响应性。该模型由三个差分方程组成的非线性系统来描述;它包含一个随机变量,并考虑到特定神经元的特征。解剖测量首先用于定位细胞体成行和定义轴突起源。然后,一个泛化过程允许从小型解剖数据集中获得单个神经元轴突的信息,用于生成更大的人工数据集。为了在轴突生长模型中指定参数,我们使用随机优化程序,推导成本函数并为每种类型的神经元找到最优参数。我们的轴突生长生物学模型从细胞体的轴突生长开始,并为每种不同的神经元类型产生多个轴突,其统计特性与真实轴突相匹配。我们说明了轴突生长模型如何适用于轴突生长到中枢神经系统的相同和相反一侧的神经元。然后,我们展示了如何通过添加树突形态的简单规范,我们的模型“发育方法”允许我们生成生物学上真实的连接体。
Relating structure and function of neuronal circuits is a challenging problem. It requires demonstrating how dynamical patterns of spiking activity lead to functions like cognitive behaviour and identifying the neurons and connections that lead to appropriate activity of a circuit. We apply a “developmental approach” to define the connectome of a simple nervous system, where connections between neurons are not prescribed but appear as a result of neuron growth. A gradient based mathematical model of two-dimensional axon growth from rows of undifferentiated neurons is derived for the different types of neurons in the brainstem and spinal cord of young tadpoles of the frog Xenopus. Model parameters define a two-dimensional CNS growth environment with three gradient cues and the specific responsiveness of the axons of each neuron type to these cues. The model is described by a nonlinear system of three difference equations; it includes a random variable, and takes specific neuron characteristics into account. Anatomical measurements are first used to position cell bodies in rows and define axon origins. Then a generalization procedure allows information on the axons of individual neurons from small anatomical datasets to be used to generate larger artificial datasets. To specify parameters in the axon growth model we use a stochastic optimization procedure, derive a cost function and find the optimal parameters for each type of neuron. Our biologically realistic model of axon growth starts from axon outgrowth from the cell body and generates multiple axons for each different neuron type with statistical properties matching those of real axons. We illustrate how the axon growth model works for neurons with axons which grow to the same and the opposite side of the CNS. We then show how, by adding a simple specification for dendrite morphology, our model “developmental approach” allows us to generate biologically-realistic connectomes.
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