Grenoble Institut des Neurosciences, Univ. Grenoble Alpes, INSERM U1216, Bat. Edmond J. Safra, Chemin F Ferrini, F-38000 Grenoble, France.
Lab Chip. 2018 Nov 6;18(22):3425-3435. doi: 10.1039/c8lc00694f.
In the central nervous system, neurons are organized in specific neural networks with distinct electrical patterns, input integration capacities, and intracellular dynamics. In order to better understand how neurons process information, it is crucial to keep the complex organization of brain circuits. However, performing subcellular investigations with high spatial and temporal resolution in vivo is technically challenging, especially in fine structures, such as axonal projections. Here, we present an on-a-chip system that combines a microfluidic platform with a dedicated matrix of electrodes to study activity-dependent dynamics in the physiological context of brain circuits. Because this system is compatible with high-resolution video-microscopy, it is possible to simultaneously record intracellular dynamics and electrical activity in presynaptic axonal projections and in their postsynaptic neuronal targets. Similarly, specific patterns of electrical activity can be applied to both compartments in order to investigate how intrinsic and network activities influence intracellular dynamics. The fluidic isolation of each compartment further allows the selective application of drugs at identified sites to study activity-dependent synaptic transmission. This integrated microfluidic/microelectrode array (microMEA) platform is a valuable tool for studying various intracellular and synaptic dynamics in response to neuronal activity in a physiologically relevant context that resembles in vivo brain circuits.
在中枢神经系统中，神经元以特定的神经网络形式组织，具有独特的电模式、输入整合能力和细胞内动力学。为了更好地理解神经元如何处理信息，保持大脑回路的复杂组织至关重要。然而，在体内进行具有高空间和时间分辨率的亚细胞研究在技术上具有挑战性，特别是在精细结构（如轴突投射）中。在这里，我们提出了一种片上系统，该系统将微流控平台与专用的电极矩阵相结合，用于研究生理条件下大脑回路中与活动相关的动力学。由于该系统与高分辨率视频显微镜兼容，因此可以同时记录细胞内动力学和突触前轴突投射及其突触后神经元靶标中的电活动。同样，可以向两个隔室施加特定模式的电活动，以研究内在和网络活动如何影响细胞内动力学。每个隔室的流体隔离进一步允许在已识别的部位选择性地应用药物，以研究活动依赖性突触传递。该集成的微流控/微电极阵列（microMEA）平台是一种有价值的工具，可用于研究各种细胞内和突触动力学，以响应类似于体内大脑回路的生理相关环境中的神经元活动。
