Stochastic simulations on the reliability of action potential propagation in thin axons.
Stochastic simulations on the reliability of action potential propagation in thin axons.
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DOI：
10.1371/journal.pcbi.0030079
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发表时间：
2007-05
影响因子：
4.3
通讯作者：
Laughlin, Simon B.
中科院分区：
文献类型：
--
作者：
Faisal, A. Aldo;Laughlin, Simon B.
一般认为，轴突使用动作电位（AP）将信息快速可靠地传递到突触。然而，沿着直径小于0.5 μm的纤维（如皮质和小脑轴突）传输的可靠性尚不清楚。使用详细的啮齿动物皮层和鱿鱼轴突和随机模拟模型，我们展示了如何传导沿着这样薄的轴突的电压门控离子通道（通道噪声）的概率性质的影响。我们确定了四个不同的影响，腐败传播尖峰列车在薄轴突：尖峰被添加，删除，抖动，或分裂成组，这取决于尖峰的时间模式。额外的AP可能会自发出现;然而，AP通常很少失败（<1%）。当传导速度以两种方式波动时，尖峰定时在毫米的距离上以毫秒的数量级抖动。首先，在AP的早期上升阶段打开的Na通道的数量的可变性导致传播速度逐渐波动。第二，一种新的AP传播模式（随机微跳跃传导），其中AP向前跳跃到自发形成的开放Na通道簇，在尖峰时间可靠性中产生随机离散跳跃。这两种机制的组合效果取决于尖峰的模式。我们的研究结果表明，轴突的变异性是一个普遍的问题，并应考虑到在密集连接的皮层网络，小突触通常由薄轴突神经支配的神经编码和突触传递的可靠性时。相比之下，我们发现直径大于0.5 μm的较厚的轴突是可靠的。大脑皮层的神经元通过使用平均直径为0.3 μm的无髓鞘轴突作为导线而实现4km/mm 3的布线密度。许多轴突（例如，疼痛纤维）更细。虽然像在计算机芯片中一样，导线微型化可以节省空间和能源，但它会增加神经元的“蛋白质晶体管”（电压门控离子通道）中热力学波动带来的噪音。我们研究了在微小轴突的膜中发现的相对少量的离子通道如何传播大脑的通用信号-动作电位。我们建立了一个随机模型，该模型结合了单个离子通道的随机行为，并发现噪声效应比以前假设的要大得多，因为标准随机近似技术（Langevin）会崩溃，因为单个通道可以产生全细胞响应。通道噪声通过随机改变传导速度来破坏动作电位时序中编码的信息，并产生一种新的传输模式，即随机微跳跃传导。离子通道群体在通道状态分布中保留先前活动的记忆，导致动作电位可靠性随环境而变化。这里确定的影响和一般关系将支配其他细胞信号传导系统，这些系统依赖于固有的噪声蛋白质开关来传播信号，无论是用于细胞内通信（Ca++/cAMP波）还是纳米技术。
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. Neurons in cerebral cortex achieve wiring densities of 4 km per mm3 by using unmyelinated axons of 0.3 μm average diameter as wires. Many axons (e.g., pain fibers) are thinner. Although, as in computer chips, wire miniaturization economizes on space and energy, it increases the noise introduced by thermodynamic fluctuations in a neuron's “protein transistors,” voltage-gated ion channels. We investigated how well the relatively small number of ion channels found in the membranes of tiny axons propagate the brain's universal signal—the action potential. We built a stochastic model that incorporates the random behavior of individual ion channels and found noise effects much larger than previously assumed, because standard stochastic approximation techniques (Langevin) break down because single channels can produce whole-cell responses. Channel noise destroys information encoded in the timing of action potentials, by randomly varying the speed of conduction, and produces a novel mode of transmission, stochastic microsaltatory conduction. Ion channel populations retain memory of previous activity in the distribution of channel states, causing action potential reliability to vary with context. The effects and general relationships identified here will govern other cell-signaling systems that rely on inherently noisy protein switches to propagate signals, either for intracellular communication (Ca++/cAMP waves) or in nanotechnology.
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影响因子：
3.4
作者：
Chow, CC;White, JA
通讯作者：
White, JA
影响因子：
5.3
作者：
Kole, MHP;Hallermann, S;Stuart, GJ
通讯作者：
Stuart, GJ
影响因子：
64.8
作者：
Hartwell, LH;Hopfield, JJ;Murray, AW
通讯作者：
Murray, AW
DOI：
10.1073/pnas.170278697
发表时间：
2000-08-15
影响因子：
11.1
作者：
Cox, CL;Denk, W;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
5.5
作者：
Jacobson, GA;Diba, K;Yarom, Y
通讯作者：
Yarom, Y