Probabilistic reachability analysis of the tap withdrawal circuit in caenorhabditis elegans

Md. Ariful Islam, Qinsi Wang, Ramin M. Hasani, Ondrej Balun, E. Clarke, R. Grosu, S. Smolka
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引用次数: 11

Abstract

We present a probabilistic reachability analysis of a (nonlinear ODE) model of a neural circuit in Caeorhabditis elegans (C. elegans), the common roundworm. In particular, we consider Tap Withdrawal (TW), a reflexive behavior exhibited by a C. elegans worm in response to vibrating the surface on which it is moving. The neural circuit underlying this response is the subject of this investigation. Specially, we perform bounded-time reachability analysis on the TW circuit model of Wicks et al. (1996) to estimate the probability of various TW responses. The Wicks et al. model has a number of parameters, and we demonstrate that the various TW responses and their probability of occurrence in a population of worms can be viewed as a problem of parameter uncertainty. Our approach to this problem rests on encoding each TW response as a hybrid automaton with parametric uncertainty. We then perform probabilistic reachability analysis on these automata using a technique that combines a δ-decision procedure with statistical tests. The results we obtain are a significant extension of those of Wicks et al. (1996), who equip their model with fixed parameter values that reproduce a single TW response. In contrast, our technique allow us to more thoroughly explore the models parameter space using statistical sampling theory, identifying in the process the distribution of TW responses. Wicks et al. conducted a number of ablation experiments on a population of worms in which one or more of the neurons in the TW circuit are surgically ablated (removed). We show that our technique can be used to correctly estimate TW response-probabilities for four of these ablation groups. We also use our technique to predict TW response behavior for two ablation groups not previously considered by Wicks et al.
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秀丽隐杆线虫抽头退出电路的概率可达性分析
我们提出了一个(非线性ODE)模型的神经回路的概率可达性分析秀丽隐杆线虫(秀丽隐杆线虫),常见的蛔虫。特别地,我们考虑了轻触撤退(TW),这是一种秀丽隐杆线虫在振动其移动的表面时表现出的反射性行为。这种反应背后的神经回路是本研究的主题。特别地,我们对Wicks等人(1996)的TW电路模型进行了有界时间可达性分析,以估计各种TW响应的概率。Wicks等人的模型有许多参数,我们证明了各种TW响应及其在蠕虫种群中发生的概率可以被视为参数不确定性问题。我们解决这个问题的方法是将每个TW响应编码为具有参数不确定性的混合自动机。然后,我们使用一种结合了δ-决策过程和统计检验的技术对这些自动机进行概率可达性分析。我们得到的结果是对Wicks等人(1996)的结果的一个重要扩展,他们为他们的模型配备了固定的参数值,这些参数值可以再现单个TW响应。相比之下,我们的技术允许我们使用统计抽样理论更彻底地探索模型参数空间,在此过程中识别TW响应的分布。Wicks等人对一群蠕虫进行了大量消融实验,其中TW回路中的一个或多个神经元被手术消融(移除)。我们表明,我们的技术可以用来正确估计四个消融组的TW响应概率。我们还使用我们的技术预测了两个消融组的TW反应行为,Wicks等人之前没有考虑过。
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