A caged neuron multielectrode system

项目总结： 这个项目的目的是建立一个研究培养的神经的系统。 网络将提供一种独特的新能力来观察每个小区的情况 连接到其他设备，以及这种连接如何变化。培养的神经元将 被关在“笼子”里，这是一种塑料结构，允许工艺扩展，但可以保持 靠近记录和刺激电极的细胞体。通过 刺激每个神经元并记录所有其他神经元的反应，连接 将会揭晓该电视网。系统将笼子放在8x8阵列中， 用光钳将分离的神经元放在笼子里。学习的能力 这种网络在单细胞层面上的细节将远远超过目前存在的任何网络。 记录和刺激不会损害神经元，因此连接可以 随着网络的发展，观察了几周的时间。非常老练 定制大规模集成电路上的电子放大器和刺激器将 它将以低成本提供研究多个笼形阵列的能力 同时，当它们在孵化器里的时候。这些研究将提供一个 有机会详细观察正常网络发展，这是前所未有的 有可能。此外，还将揭示强制模拟对网络的影响， 从几小时到几周的时间尺度上。对连接的药理作用也将是 可观察到的。最后，因为它们被关在笼子里，所以细胞类型可以混合放置在 已知的位置，以便在它们形成网络时它们之间特定类型的交互 将是可观察到的。一个最有趣的例子是观察 胚胎干细胞来源的神经元与正常神经元网络。作为证明 概念在这项研究结束时，这样的实验将开始。它们将指示 在移植中干细胞-神经元-神经元与正常细胞整合的潜力，也将 为研究如何促进这种融合提供机会。

Project Summary: The aim of this project is to create a system for studying cultured neural networks that will provide a unique new ability for observing how each cell is connected to the others and how that connectivity changes. The cultured neurons will be in "cages" that are plastic structures which allow process outgrowth but maintain the cell body in close proximity to a recording and stimulating electrode. By stimulating each neuron and recording the responses of all the others, the connectivity of the network will be revealed. The system will have 64 cages in an 8 x 8 array, with 64 dissociated neurons placed in cages using an optical tweezers. The capability to study such networks in detail at the single cell level will be far beyond any that now exists. Recording and stimulation do not damage the neurons, so the connectivity can be observed over a period of weeks, as the network develops. Very sophisticated electronic amplifiers and stimulators on custom large scale integrated circuits will be used, which will provide at low cost the capability of studying multiple caged arrays simultaneously, while they are in an incubator. The studies will provide an opportunity to observe normal network development in detail that has never been possible. In addition, the effects on networks of imposed simulation will be revealed, on time scales of hours to weeks. Pharmacological effects on connectivity will also be observable. Lastly, because they are in cages, cell types can be mixed and placed in known locations, so that type-specific interactions between them as they form networks will be observable. A most interesting example will be to observe the interaction of embryonic-stem-cell derived neurons with networks of normal neurons. As a proof of concept at the end of this study, such experiments will be begun. They will indicate the potential for stem-cell-neuron integration with normal cells in transplants, and also will provide opportunities for studying how to promote that integration.