Functional Characterization of Three-Dimensional Cortical Cultures for In Vitro Modeling of Brain Networks
Functional Characterization of Three-Dimensional Cortical Cultures for In Vitro Modeling of Brain Networks
复制标题
DOI：
10.1016/j.isci.2020.101434
复制
发表时间：
2020-08-21
期刊：
影响因子：
5.8
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
--
作者：
Dingle, Yu-Ting L.;Liaudanskaya, Volha;Kaplan, David L.
三维（3D）体外培养概括了脑的关键特征，包括形态学、细胞-细胞和细胞-细胞外基质相互作用、因子梯度和机械特性。然而，仍然需要实验和计算工具来研究这些3D模型中的网络功能。为了解决这一需求，我们提出了一种基于3D支架的皮层神经元培养物的实验系统，其中我们表达了遗传编码的钙指示剂GCaMP 6 f，以记录毫米级的神经元活动。用基于图论的网络分析方法计算功能性神经网络描述符，显示培养3周时功能性网络的形成。对海马能神经传递或γ-氨基丁酸能神经传递受到干扰时功能网络性质的变化进行了定量表征。结果表明，我们的3D实验系统的适用性，在仿生微环境中的大脑网络的发展，功能和破坏的研究。
Three-dimensional (3D) in vitro cultures recapitulate key features of the brain including morphology, cell-cell and cell-extracellular matrix interactions, gradi-ents of factors, and mechanical properties. However, there remains a need for experimental and computational tools to investigate network functions in these 3D models. To address this need, we present an experimental system based on 3D scaffold-based cortical neuron cultures in which we expressed the genetically encoded calcium indicator GCaMP6f to record neuronal activity at the millimeter -scale. Functional neural network descriptors were computed with graph-theory -based network analysis methods, showing the formation of functional networks at 3 weeks of culture. Changes to the functional network properties upon pertur-bations to glutamatergic neurotransmission or GABAergic neurotransmission were quantitatively characterized. The results illustrate the applicability of our 3D experimental system for the study of brain network development, function, and disruption in a biomimetic microenvironment.