Objective. The goal of this work is to develop and characterize an innovative experimental framework to design interconnected (i.e. modular) heterogeneous (cortical-hippocampal) neuronal cultures with a three-dimensional (3D) connectivity and to record their electrophysiological activity using micro-electrode arrays (MEAs). Approach. A two-compartment polymeric mask for the segregation of different neuronal populations (cortex and hippocampus) was coupled to the MEA surface. Glass microbeads were used as a scaffold to mimic the 3D brain micro-architecture. Main results. We built a fully functional heterogeneous 3D neuronal network. From an electrophysiological point of view, we found that the heterogeneity induces a global increase of the activity rate, while the 3D connectivity modulates the duration and the organization of the bursting activity. Significance. In vivo, studies of network dynamics and interactions between neuronal populations are often time-consuming, low-throughput, complex, and suffer from reproducibility. On the other hand, most of the commonly used in vitro brain models are too simplified and thus far from the in vivo situation. The achieved results demonstrate the feasibility to build a more realistic and controllable experimental in vitro model of interconnected brain regions on-a-chip whose applications may have impacts on the study of neurological disorders that impair the connectivity between brain areas (e.g. Parkinson disease).

客观的。这项工作的目标是开发和表征一个创新的实验框架，以设计具有三维（3D）连通性的互连（即模块化）异质（皮质-海马）神经元培养物，并使用微电极阵列记录它们的电生理活动。多边环境协定）。方法。用于分离不同神经元群（皮层和海马）的两室聚合物面罩与 MEA 表面耦合。玻璃微珠被用作支架来模拟 3D 大脑微结构。主要结果。我们构建了一个功能齐全的异构 3D 神经元网络。从电生理学的角度来看，我们发现异质性导致活动率的整体增加，而 3D 连接调节爆发活动的持续时间和组织。意义。在体内，神经元群之间的网络动力学和相互作用的研究通常耗时、低通量、复杂且存在可重复性。另一方面，大多数常用的体外脑模型过于简化，与体内情况相差甚远。取得的成果证明了建立更真实可控的体外实验的可行性 芯片上相互连接的大脑区域模型，其应用可能会对损害大脑区域之间连接的神经系统疾病（例如帕金森病）的研究产生影响。