Cortical Axons, Isolated in Channels, Display Activity-Dependent Signal Modulation as a Result of Targeted Stimulation.
Cortical Axons, Isolated in Channels, Display Activity-Dependent Signal Modulation as a Result of Targeted Stimulation.
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DOI：
10.3389/fnins.2016.00083
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发表时间：
2016
影响因子：
4.3
通讯作者：
Hierlemann AR
中科院分区：
文献类型：
--
作者：
Lewandowska MK;Radivojević M;Jäckel D;Müller J;Hierlemann AR
哺乳动物皮质轴突是非常薄的过程，由于其直径小，很难研究：它们太窄而无法完整修补，并且需要超分辨率显微镜来解析单个轴突。我们提出了一种研究轴突生理学的方法，通过配对的高密度微电极阵列与微流控轴突分离装置，并使用它来研究轴突信号传播诱发附近的索马刺激的活性依赖性调制。从一个单一的神经元，在不同的通道隔离，多达三个轴突分支，同时使用10-20个电极每个通道记录。轴突通道放大尖峰，使得可以容易地以高信噪比辨别个体信号沿沿着数十个电极的传播。从10到160 Hz的刺激表明，所有研究的细胞都有类似的定性结果：细胞外动作电位特性对刺激的反应发生了急剧变化。随着刺激次数和刺激频率的增加，作为传播速度降低的结果，尖峰高度降低，尖峰宽度增加，潜伏期增加。定量地说，这些变化的强度在不同频率的刺激下在细胞中表现不同。一些细胞的信号保真度在10 Hz时已经下降到80%，而另一些细胞在80 Hz时保持80%的信号保真度。同样的细胞的轴突分支的调制的差异，也看到了不同的刺激频率，从10 Hz开始。钾离子浓度的变化改变了细胞的行为，在较低浓度下引起繁殖失败，在较高浓度下改善信号保真度。
Mammalian cortical axons are extremely thin processes that are difficult to study as a result of their small diameter: they are too narrow to patch while intact, and super-resolution microscopy is needed to resolve single axons. We present a method for studying axonal physiology by pairing a high-density microelectrode array with a microfluidic axonal isolation device, and use it to study activity-dependent modulation of axonal signal propagation evoked by stimulation near the soma. Up to three axonal branches from a single neuron, isolated in different channels, were recorded from simultaneously using 10–20 electrodes per channel. The axonal channels amplified spikes such that propagations of individual signals along tens of electrodes could easily be discerned with high signal to noise. Stimulation from 10 up to 160 Hz demonstrated similar qualitative results from all of the cells studied: extracellular action potential characteristics changed drastically in response to stimulation. Spike height decreased, spike width increased, and latency increased, as a result of reduced propagation velocity, as the number of stimulations and the stimulation frequencies increased. Quantitatively, the strength of these changes manifested itself differently in cells at different frequencies of stimulation. Some cells' signal fidelity fell to 80% already at 10 Hz, while others maintained 80% signal fidelity at 80 Hz. Differences in modulation by axonal branches of the same cell were also seen for different stimulation frequencies, starting at 10 Hz. Potassium ion concentration changes altered the behavior of the cells causing propagation failures at lower concentrations and improving signal fidelity at higher concentrations.