An axon initial segment is required for temporal precision in action potential encoding by neuronal populations.

An axon initial segment is required for temporal precision in action potential encoding by neuronal populations.
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DOI:
10.1126/sciadv.aau8621
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发表时间:
2018-11
期刊:
影响因子:
13.6
通讯作者:
Neef A
Neef A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Lazarov E;Dannemeyer M;Feulner B;Enderlein J;Gutnick MJ;Wolf F;Neef A

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轴突初始段的关键特征是离子通道的聚类,这有助于神经网络中的信息编码。中枢神经元在轴突初始段(AIS)启动动作电位(APs),这是一个以高浓度电压依赖性离子通道和以规则纳米级模式排列的特化细胞骨架锚定蛋白为特征的隔室。尽管AIS是神经元的一个关键进化创新,但它所带来的功能益处尚不清楚。利用AIS细胞骨架蛋白β iv -谱蛋白的突变,我们在这里建立了一个具有受干扰AIS结构的神经元体外模型,该模型保留了纳米级秩序,但失去了维持高NaV密度的能力。结合实验和模拟,我们发现AIS中高NaV密度并不需要轴突AP的启动;然而,它对于高带宽的信息编码和AP定时精度至关重要。我们的研究结果首次提供了在没有高轴突通道密度的情况下轴突AP启动的实验证明,并表明增加神经元编码的带宽,从而提高网络函数的计算效率,是AIS进化的一个主要好处。
The key feature of the axon initial segment, clustering of ion channels, facilitates information encoding in neuronal networks. Central neurons initiate action potentials (APs) in the axon initial segment (AIS), a compartment characterized by a high concentration of voltage-dependent ion channels and specialized cytoskeletal anchoring proteins arranged in a regular nanoscale pattern. Although the AIS was a key evolutionary innovation in neurons, the functional benefits it confers are not clear. Using a mutation of the AIS cytoskeletal protein βIV-spectrin, we here establish an in vitro model of neurons with a perturbed AIS architecture that retains nanoscale order but loses the ability to maintain a high NaV density. Combining experiments and simulations, we show that a high NaV density in the AIS is not required for axonal AP initiation; it is, however, crucial for a high bandwidth of information encoding and AP timing precision. Our results provide the first experimental demonstration of axonal AP initiation without high axonal channel density and suggest that increasing the bandwidth of the neuronal code and, hence, the computational efficiency of network function, was a major benefit of the evolution of the AIS.
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