Sharpness of spike initiation in neurons explained by compartmentalization.
Sharpness of spike initiation in neurons explained by compartmentalization.
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DOI：
10.1371/journal.pcbi.1003338
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发表时间：
2013
影响因子：
4.3
通讯作者：
Brette R
中科院分区：
文献类型：
--
作者：
Brette R
在皮层神经元中，尖峰起始于轴突起始段。从索马看，它们显得出奇地锋利。一个标准的解释是，当尖峰信号被积极地反向传播到索马时，来自轴突的电流变得尖锐。然而，尖峰的急剧启动也见于神经元的输入-输出特性，而不仅仅是尖峰的躯体形状;例如，皮层神经元可以传输高频信号。另一种假设是Na通道合作，但目前没有直接的实验证据支持。我提出了一个简单的解释的基础上划分的尖峰启动。当Na通道被放置在轴突中时，索马充当Na电流的电流槽。我表明，有一个临界距离的索马以上的不稳定性发生，使钠通道突然打开，而不是逐渐作为体细胞电压的函数。尖峰起始决定了神经元的组合输入如何转换为输出。自从Hodgkin和Huxley的开创性工作以来，已知尖峰是由钠通道的去极化开放产生的。根据这一标准理论，当膜电位增加时，这些通道应该逐渐打开，但在索马测量到的尖峰似乎从静止状态突然上升。这一明显的矛盾引发了一场关于穗“锋利”起源的争论。这项研究表明，与生物物理模型，如果钠通道被放置在轴突，而不是在索马，他们打开时，体细胞膜电位超过一个临界值。这项工作解释了尖峰启动的尖锐性，并提供了另一个证据，形态在神经功能中起着至关重要的作用。
In cortical neurons, spikes are initiated in the axon initial segment. Seen at the soma, they appear surprisingly sharp. A standard explanation is that the current coming from the axon becomes sharp as the spike is actively backpropagated to the soma. However, sharp initiation of spikes is also seen in the input–output properties of neurons, and not only in the somatic shape of spikes; for example, cortical neurons can transmit high frequency signals. An alternative hypothesis is that Na channels cooperate, but it is not currently supported by direct experimental evidence. I propose a simple explanation based on the compartmentalization of spike initiation. When Na channels are placed in the axon, the soma acts as a current sink for the Na current. I show that there is a critical distance to the soma above which an instability occurs, so that Na channels open abruptly rather than gradually as a function of somatic voltage. Spike initiation determines how the combined inputs to a neuron are converted to an output. Since the pioneering work of Hodgkin and Huxley, it is known that spikes are generated by the opening of sodium channels with depolarization. According to this standard theory, these channels should open gradually when the membrane potential increases, but spikes measured at the soma appear to suddenly rise from rest. This apparent contradiction has triggered a controversy about the origin of spike “sharpness.” This study shows with biophysical modelling that if sodium channels are placed in the axon rather than in the soma, they open all at once when the somatic membrane potential exceeds a critical value. This work explains the sharpness of spike initiation and provides another demonstration that morphology plays a critical role in neural function.
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