Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 0213, USA.
Univ. Grenoble Alpes, LTM, F-38000 Grenoble, France.
Sci Rep. 2016 Jun 22;6:28384. doi: 10.1038/srep28384.
The central nervous system is a dense, layered, 3D interconnected network of populations of neurons, and thus recapitulating that complexity for in vitro CNS models requires methods that can create defined topologically-complex neuronal networks. Several three-dimensional patterning approaches have been developed but none have demonstrated the ability to control the connections between populations of neurons. Here we report a method using AC electrokinetic forces that can guide, accelerate, slow down and push up neurites in un-modified collagen scaffolds. We present a means to create in vitro neural networks of arbitrary complexity by using such forces to create 3D intersections of primary neuronal populations that are plated in a 2D plane. We report for the first time in vitro basic brain motifs that have been previously observed in vivo and show that their functional network is highly decorrelated to their structure. This platform can provide building blocks to reproduce in vitro the complexity of neural circuits and provide a minimalistic environment to study the structure-function relationship of the brain circuitry.
中枢神经系统是一个密集的、分层的、三维相互连接的神经元群体网络，因此为体外中枢神经系统模型再现这种复杂性需要能够创建定义明确的拓扑复杂神经元网络的方法。已经开发了几种三维图案形成方法，但没有一种方法能够证明其能够控制神经元群体之间的连接。在这里，我们报告了一种使用交流电动力量的方法，该方法可以引导、加速、减缓和推动未修饰的胶原支架中的神经突。我们提出了一种通过使用这种力在 2D 平面上种植的初级神经元群体中创建 3D 交点来创建任意复杂程度的体外神经网络的方法。我们首次在体外报告了以前在体内观察到的基本脑模式，并表明它们的功能网络与其结构高度不相关。该平台可以提供构建模块，以在体外重现神经网络的复杂性，并提供一个极简主义的环境来研究大脑电路的结构-功能关系。
