持续刺激下神经传递中的限速恢复过程
Rate-limiting recovery processes in neurotransmission under sustained stimulation
AI总结：
本文通过构建包含囊泡与释放位点恢复步骤的非线性反应网络及其ODE和随机跳跃模型，研究持续刺激下神经传递的限速因素，发现限速特征随刺激过程动态变化而非固定于单一恢复步骤。
摘要：
在化学突触中，到达的电信号诱导囊泡与突触前膜融合，从而将神经递质释放到突触间隙中。融合事件发生后，释放位点和囊泡都要经历一个恢复过程，然后才能再次被重新使用。核心关注的问题是：在高频持续刺激下的神经传递过程中，这两个恢复步骤中哪一个构成限制因素。为了研究这一问题，我们引入了一个新颖的非线性反应网络，该网络包含囊泡和释放位点的显式恢复步骤，并纳入了诱导产生的随时间变化的输出电流。相关的反应动力学通过常微分方程（ODEs）以及相应的随机跳跃过程来表述。随机跳跃模型描述单个释放位点，而许多释放位点的平均值接近 ODE 解，并共享其周期结构。其原因可以追溯到这样一个见解：囊泡和释放位点的恢复动力学在统计上几乎相互独立。基于 ODE 表述对恢复速率进行的敏感性分析表明，既不能将囊泡恢复步骤也不能将释放位点恢复步骤确定为本质上的限速步骤，而是限速特征在刺激过程中会发生变化。在持续刺激下，由 ODE 给出的动力学表现出瞬态变化，从突触后响应的初始抑制过渡到一个渐近周期轨道，而随机跳跃模型的个体轨迹则缺乏 ODE 解的振荡行为和渐近周期性。
英文摘要：
At chemical synapses, an arriving electric signal induces the fusion of vesicles with the presynaptic membrane, thereby releasing neurotransmitters into the synaptic cleft. After a fusion event, both the release site and the vesicle undergo a recovery process before becoming available for reuse again. Of central interest is the question which of the two restoration steps acts as the limiting factor during neurotransmission under high-frequency sustained stimulation. In order to investigate this question, we introduce a novel non-linear reaction network which involves explicit recovery steps for both the vesicles and the release sites, and includes the induced time-dependent output current. The associated reaction dynamics are formulated by means of ordinary differential equations (ODEs), as well as via the associated stochastic jump process. While the stochastic jump model describes a single release site, the average over many release sites is close to the ODE solution and shares its periodic structure. The reason for this can be traced back to the insight that recovery dynamics of vesicles and release sites are statistically almost independent. A sensitivity analysis on the recovery rates based on the ODE formulation reveals that neither the vesicle nor the release site recovery step can be identified as the essential rate-limiting step but that the rate-limiting feature changes over the course of stimulation. Under sustained stimulation the dynamics given by the ODEs exhibit transient changes leading from an initial depression of the postsynaptic response to an asymptotic periodic orbit, while the individual trajectories of the stochastic jump model lack the oscillatory behavior and asymptotic periodicity of the ODE-solution.
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