Stochastic Simulations on the Reliability of Action Potential Propagation in Thin Axons

It is generally assumed that axons use action potentials (APs) to transmit information fast and reliably to synapses. Yet, the reliability of transmission along fibers below 0.5 μm diameter, such as cortical and cerebellar axons, is unknown. Using detailed models of rodent cortical and squid axons and stochastic simulations, we show how conduction along such thin axons is affected by the probabilistic nature of voltage-gated ion channels (channel noise). We identify four distinct effects that corrupt propagating spike trains in thin axons: spikes were added, deleted, jittered, or split into groups depending upon the temporal pattern of spikes. Additional APs may appear spontaneously; however, APs in general seldom fail (<1%). Spike timing is jittered on the order of milliseconds over distances of millimeters, as conduction velocity fluctuates in two ways. First, variability in the number of Na channels opening in the early rising phase of the AP cause propagation speed to fluctuate gradually. Second, a novel mode of AP propagation (stochastic microsaltatory conduction), where the AP leaps ahead toward spontaneously formed clusters of open Na channels, produces random discrete jumps in spike time reliability. The combined effect of these two mechanisms depends on the pattern of spikes. Our results show that axonal variability is a general problem and should be taken into account when considering both neural coding and the reliability of synaptic transmission in densely connected cortical networks, where small synapses are typically innervated by thin axons. In contrast we find that thicker axons above 0.5 μm diameter are reliable.

学界普遍认为，轴突（axon）依靠动作电位（action potentials, APs）向突触（synapse）快速且可靠地传递信息。然而，直径小于0.5 μm的神经纤维（如皮层轴突与小脑轴突）的信号传导可靠性仍未明确。本研究借助啮齿类皮层轴突与枪乌贼轴突的详细模型，并结合随机模拟，揭示了电压门控离子通道（voltage-gated ion channels）的概率特性（即通道噪声（channel noise））对这类细轴突信号传导的影响。我们明确了四种会破坏细轴突内锋电位序列（spike trains）传播的不同效应：根据锋电位的时间发放模式，锋电位会出现新增、缺失、时序抖动，或被分组为簇。额外的动作电位可能自发产生，但总体而言，动作电位的传导失败率极低（<1%）。由于传导速度存在两种波动模式，锋电位时序会在毫米级的传导距离上产生毫秒级的抖动。其一，动作电位上升早期开放的钠通道（Na channels）数量存在差异，导致传导速度逐渐波动；其二，我们发现了一种全新的动作电位传导模式——随机微跳跃传导（stochastic microsaltatory conduction）：动作电位会向自发形成的开放钠通道簇跳跃前进，这会导致锋电位时序可靠性出现随机的离散跳变。这两种机制的综合效应取决于锋电位的发放模式。本研究结果表明，轴突传导的变异性是一个普遍存在的问题，在研究密集连接皮层网络中的神经编码（neural coding）与突触传递（synaptic transmission）可靠性时必须予以考虑——此类网络中的小型突触通常由细轴突支配。与之相反，直径大于0.5 μm的粗轴突则具有可靠的传导特性。