Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability.
Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability.
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在神经元中，轴突起始段（AIS）是轴突起始附近的一个专门区域，是动作电位起始的部位。AIS的精确位置在不同的神经元类型之间和不同的神经元类型内部都有所不同，并且与细胞的信息处理能力有关;然而，决定AIS在单个神经元中位置的因素仍然未知。在这里，我们表明，电活动的变化可以改变AIS的位置。在分离的海马培养物中，高钾的慢性去极化使AIS的多个组分（包括电压门控钠通道）移动到离兴奋性神经元的索马体17 μm远。当神经元返回到非去极化状态时，这种运动逆转，并且取决于T型和/或L型电压门控钙通道的激活。当我们将长期LED（发光二极管）光刺激与光激活阳离子通道channelrhodopsin-2的稀疏神经元表达相结合时，AIS也向远端移动;在这里，在相同频率的常规刺激失败的情况下，活动的突发模式是成功的。此外，AIS位置的变化与动作电位尖峰电流阈值的改变相关。我们的研究结果表明，神经元可以调节整个亚细胞结构的位置，根据他们正在进行的水平和模式的电活动。这种新形式的活动依赖性可塑性可能微调神经元的兴奋性在发展过程中。
In neurons, the axon initial segment (AIS) is a specialised region near the start of the axon that is the site of action potential initiation. The precise location of the AIS varies across and within different neuronal types, and has been linked to cells’ information-processing capabilities; however, the factors determining AIS position in individual neurons remain unknown. Here we show that changes in electrical activity can alter the location of the AIS. In dissociated hippocampal cultures, chronic depolarization with high potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 μm away from the soma of excitatory neurons. This movement reverses when neurons are returned to non-depolarized conditions, and depends upon the activation of T- and/or L-type voltage-gated calcium channels. The AIS also moved distally when we combined long-term LED (light-emitting diode) photostimulation with sparse neuronal expression of the light-activated cation channel channelrhodopsin-2; here, burst patterning of activity was successful where regular stimulation at the same frequency failed. Furthermore, changes in AIS position correlate with alterations in current thresholds for action potential spiking. Our results show that neurons can regulate the position of an entire subcellular structure according to their ongoing levels and patterns of electrical activity. This novel form of activity-dependent plasticity may fine-tune neuronal excitability during development.
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