Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Kavli Institute for Systems Neuroscience, Centre for Neural Computation, Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
Sci Rep. 2024 Oct 29;14(1):26021. doi: 10.1038/s41598-024-77157-4.
Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing this device with nanoporous microelectrodes, we show that the reverse engineered multinodal neural networks exhibit capacity for both segregated and integrated functional activity, mimicking brain network dynamics. To advocate the broader applicability of our model system, we induced localized perturbations with amyloid beta to study the impact of pathology on network functionality. Additionally, we demonstrate long-term culturing of subregion- and layer specific neurons extracted from the entorhinal cortex and hippocampus of adult Alzheimer's-model mice and rats. Our results thus highlight the potential of our approach for reverse engineering of anatomically relevant multinodal neural networks to study dynamic structure-function relationships in both healthy and pathological conditions.
工程化生物神经网络是从亚细胞到网络水平研究神经功能和功能障碍不可或缺的模型。值得注意的是，先进的神经工程方法具有复制大脑网络的拓扑和功能组织的潜力，因此受到了极大的关注。在这项研究中，我们使用具有特斯拉阀启发的微隧道的定制多节点微流控设备，对原代皮质和海马神经元的前馈神经网络进行了反向工程。通过将该设备与纳米多孔微电极接口，我们证明了反向工程的多节点神经网络具有隔离和集成功能活动的能力，模拟了大脑网络动力学。为了提倡我们的模型系统更广泛的适用性，我们用淀粉样β诱导局部扰动，研究病理学对网络功能的影响。此外，我们还展示了从成年阿尔茨海默病模型小鼠和大鼠的内嗅皮层和海马体中提取的亚区和层特异性神经元的长期培养。因此，我们的结果强调了我们的方法在反向工程解剖相关多节点神经网络以研究健康和病理条件下动态结构-功能关系方面的潜力。
