Electrokinetic confinement of axonal growth for dynamically configurable neural networks
Electrokinetic confinement of axonal growth for dynamically configurable neural networks
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DOI：
10.1039/c2lc41000a
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发表时间：
2013-01-01
期刊：
影响因子：
6.1
通讯作者：
Voldman, Joel
中科院分区：
文献类型：
--
作者：
Honegger, Thibault;Scott, Mark A.;Voldman, Joel
发育中的神经系统中的轴突通过引导线索进行引导，其表达在空间和时间上都有所不同，以创建功能性神经回路。现有的体外创建神经连接模式的方法仅使用静态几何形状，并且无法动态改变传递给细胞的引导线索。我们介绍了使用交流电动力学来动态控制培养的大鼠海马神经元的轴突生长。我们发现，以 10(5) Hz 的频率施加适度的电压可以导致正在发育的轴突在电极附近停止，而远离电场的轴突则表现出不受抑制的生长。通过打开或关闭电极，我们可以可逆地抑制或允许轴突穿过电极。我们的模型表明介电泳是交流电动效应的起因。我们利用对轴突伸长的动态控制，通过轴突锁定系统创建轴突二极管，该系统由一对电极“门”组成，允许或阻止轴突通过。最后，我们开发了一个由三个神经元群组成的神经回路，由三个轴突锁分隔开，以演示功能性工程神经网络的组装。动作电位记录表明交流电动效应不会损害轴突，Ca2+ 成像证明了突触连接的单向性质。轴突生长的交流电动限制具有创建可配置的定向神经网络的潜力。
Axons in the developing nervous system are directed via guidance cues, whose expression varies both spatially and temporally, to create functional neural circuits. Existing methods to create patterns of neural connectivity in vitro use only static geometries, and are unable to dynamically alter the guidance cues imparted on the cells. We introduce the use of AC electrokinetics to dynamically control axonal growth in cultured rat hippocampal neurons. We find that the application of modest voltages at frequencies on the order of 10(5) Hz can cause developing axons to be stopped adjacent to the electrodes while axons away from the electric fields exhibit uninhibited growth. By switching electrodes on or off, we can reversibly inhibit or permit axon passage across the electrodes. Our models suggest that dielectrophoresis is the causative AC electrokinetic effect. We make use of our dynamic control over axon elongation to create an axon-diode via an axon-lock system that consists of a pair of electrode 'gates' that either permit or prevent axons from passing through. Finally, we developed a neural circuit consisting of three populations of neurons, separated by three axon-locks to demonstrate the assembly of a functional, engineered neural network. Action potential recordings demonstrate that the AC electrokinetic effect does not harm axons, and Ca2+ imaging demonstrated the unidirectional nature of the synaptic connections. AC electrokinetic confinement of axonal growth has potential for creating configurable, directional neural networks.