AI 中文总结
本研究提出两层分析框架，构建带暂停的持久电报过程半马尔可夫模型，揭示神经元中mRNA转运的MFPT与持久方向、树突长度的关系。
AI 中文摘要
本文提出了一个用于建模信使核糖核酸（mRNA）分子沿神经元微管从胞体向突触转运的两层分析框架。受mRNA货物运动的实验观察结果启发，树突内的转运被建模为带有暂停的持久电报过程。针对持久概率不同和相等的情况，推导了穿越树突的概率及此类运动平均时间的理论表达式。这些结果被用于构建整个神经元内mRNA货物运动的半马尔可夫模型，该模型提供了从转录mRNA的胞体到给定突触的吸收概率及相应的平均首次通过时间（MFPT）。结合实验获得的参数值，利用这些理论表达式计算了具有实验重构形态的神经元的MFPT。该模型预测，当逆行持久力更强时，到达每个突触的MFPT基本相同；否则，当顺行方向的持久力更显著时，神经元内的转运类似于沿单个树突的运动——MFPT与胞体和突触之间的距离呈近线性依赖关系。当树突长度远大于典型运动行程的距离时，这些发现得到理论验证。
英文摘要
A two-level analytical framework is presented for modeling random walk transport of messenger ribonucleic acid (mRNA) molecules along neuronal microtubules from soma to synapses. Motivated by empirical observations of mRNA cargo motion, the transport within a dendrite is modeled by a persistent telegraph process with pauses. Theoretical expressions for the probability of traversing the dendrite and the mean time for such travel are derived for different and equal probabilities of persistence. These results are used for the construction of a semi-Markov model of motion of mRNA cargo within the whole neuron. The semi-Markov model provides the probabilities of absorption at a given synapse and corresponding mean first-passage times (MFPTs) from the soma, where mRNA is transcribed. The theoretical expressions, together with experimentally obtained parameter values, are used to calculate MFPTs for neurons with empirically reconstructed morphology. The model predicts that when retrograde persistence is stronger, the MFPT to each synapse is effectively the same. Otherwise, when the persistence is more pronounced in the anterograde direction, the transport in the neuron resembles the motion along a single dendrite -- nearly linear dependence of MFPT on the distance between soma and synapse. These findings are theoretically justified when the lengths of dendrites are considerably longer than the distance traversed during a typical run.
