Changes in Functional Network Output of Cocultured Ventral Horn Neurons

Co-cultures are a traditional method for studying the cellular properties of cell to cell interactions among different cell types. How network properties in these multicellular synthetic systems vary from monocultures are of particular interest. Understanding the changes in the functional output of these in vitro spiking neural networks can provide new insights into in vivo systems and how to develop biological system models that better reflect physiological conditions - something of paramount importance to the progress of synthetic biology. Culture models of spinal motor neurons have been customarily studied as a monoculture, and the overwhelming consensus is that in culture they are different in nature from their in vivo counterparts. We studied the electrophysiological properties of spinal ventral horn networks cocultured with myocytes or astrocytes using a 64 channel microelectrode array system to record extracellular voltage measurements. Significant differences were found between coculture types in metrics of spiking, bursting, and network bursting. Traditional culturing techniques involving a uniform cell type might not be the best way to functionally model in vivo neural networks. A synthetic ecosystem of various cell types is beneficial to replicating cell behavior in vitro, thus is a necessary refinement to the commonly used technique of cell culture. With a more physiological model system, hypotheses about interacting systems can be better addressed and the outcomes will have greater relevancy.

共培养技术是研究不同细胞类型间细胞相互作用的细胞特性的一种传统方法。探讨这些多细胞合成系统中网络特性与单细胞培养之间的差异，具有特殊意义。对这些体外突触神经网络功能输出的变化进行理解，能够为体内系统提供新的洞见，并有助于开发更贴合生理条件的生物系统模型，这对合成生物学的发展至关重要。脊髓运动神经元的培养模型通常被作为单细胞培养进行研究，普遍认为在培养条件下，它们在本质上与其体内对应物存在差异。我们利用64通道微电极阵列系统，对与肌细胞或星形胶质细胞共培养的脊髓背角网络进行电生理特性研究，记录了细胞外电压测量值。在共培养类型中，我们发现突触、爆发和网络爆发等指标存在显著差异。传统的涉及单一细胞类型的培养技术可能并非是功能模拟体内神经网络的最佳途径。构建包含各种细胞类型的合成生态系统，有助于在体外复制细胞行为，因此是对常规细胞培养技术的一种必要改进。通过更符合生理的模型系统，可以更好地解决关于相互作用系统的假设，并且研究结果将具有更高的相关性。