Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity
Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity
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DOI：
10.1073/pnas.1607541114
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发表时间：
2017-02-07
影响因子：
11.1
通讯作者：
Nagerl, U. Valentin
中科院分区：
文献类型：
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作者：
Chereau, Ronan;Saraceno, G. Ezequiel;Nagerl, U. Valentin
轴突将信息传递到附近和远处的细胞，动作电位（AP）到达目标所需的时间决定了神经回路中信息传递的时间。在海马的无髓鞘轴突中，AP的传导速度关键取决于轴突直径，其变化很大。然而，目前尚不清楚轴突直径是否是动态的，并通过活动依赖性机制进行调节。我们在脑切片中使用延时超分辨率显微镜，报告了高频AP放电后轴突变得更宽：突触终扣经历快速扩大，这大多是短暂的，而轴突轴的直径显示出更延迟和渐进的增加。AP传播的模拟结合这些形态学动力学预测双向影响AP传导速度。这些预测得到了电生理学实验的证实，揭示了一个减缓AP传导的阶段，这与突触终扣的瞬时扩大有关，随后伴随着高频AP放电引起的轴突轴变宽的传导速度持续增加。总之，我们的研究概述了形态可塑性机制，动态微调AP传导速度，这可能有广泛的影响，在大脑中的信息的时间转移。
Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.