Structural and Functional Refinement of the Axon Initial Segment in Avian Cochlear Nucleus during Development
Structural and Functional Refinement of the Axon Initial Segment in Avian Cochlear Nucleus during Development
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DOI：
10.1523/jneurosci.3068-19.2020
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发表时间：
2020-08-26
影响因子：
5.3
通讯作者：
Kuba, Hiroshi
中科院分区：
文献类型：
--
作者：
Akter, Nargis;Fukaya, Ryota;Kuba, Hiroshi
轴突起始段（AIS）参与动作电位的起始。AIS的结构和生物物理特征在细胞类型和/或脑区域之间存在差异，但其潜在机制尚不清楚。利用免疫荧光和电生理方法，结合超分辨率成像，我们发现在发育中的鸡的雌雄大细胞核中，AIS以一种张力区域依赖的方式被改进。在调谐到不同频率的细胞中，AIS的改进过程是不同的。在听力开始时，AIS类似于50 μ m长，几乎没有电压门控钠通道，无论张力区域如何。然而，在孵化后，AIS成熟并呈现出-20 μ m长的结构，其中钠通道显著富集，导致钠电流增加和尖峰阈值降低。此外，在调谐到更高频率的神经元中，缩短更为明显，而通道的积累则没有，从而在AIS中产生张力异位差异。我们得出结论，AIS缩短是由AIS远端细胞骨架的解体介导的，尽管AIS上的亚膜细胞骨架具有完整的周期性。重要的是，剥夺传入输入在很大程度上减少了后草动物神经元的缩短，而对钠离子通道的积累几乎没有影响。因此，AIS的细胞骨架重组和钠通道富集受到不同张力区域的差异调节，但协同工作以优化听核的神经元输出。
The axon initial segment (AIS) is involved in action potential initiation. Structural and biophysical characteristics of the AIS differ among cell types and/or brain regions, but the underlying mechanisms remain elusive. Using immunofluorescence and electrophysiological methods, combined with super-resolution imaging, we show in the developing nucleus magnocellularis of the chicken in both sexes that the AIS is refined in a tonotopic region-dependent manner. This process of AIS refinement differs among cells tuned to different frequencies. At hearing onset, the AIS was similar to 50 mu m long with few voltage-gated sodium channels regardless of tonotopic region. However, after hatching, the AIS matured and displayed an -20-mu m-long structure with a significant enrichment of sodium channels responsible for an increase in sodium current and a decrease in spike threshold. Moreover, the shortening was more pronounced, while the accumulation of channels was not, in neurons tuned to higher frequency, creating tonotopic differences in the AIS. We conclude that AIS shortening is mediated by disassembly of the cytoskeleton at the distal end of the AIS, despite intact periodicity of the submembranous cytoskeleton across the AIS. Importantly, deprivation of afferent input diminished the shortening in neurons tuned to a higher frequency to a larger extent in posthatch animals, with little effect on the accumulation of sodium channels. Thus, cytoskeletal reorganization and sodium channel enrichment at the AIS are differentially regulated depending on tonotopic region, but work synergistically to optimize neuronal output in the auditory nucleus.