A caged neuron multielectrode system

笼式神经元多电极系统

基本信息

批准号：
8289108
负责人：
JEROME PINE
金额：
$ 23.51万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-01 至 2013-12-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The capability for studying cultured networks that this project provides will provide important new data on network development, plasticity, and pharmacological responses. This will be relevant to medical applications that ameliorate neurological problems using chronic stimulation and drugs. In addition, the experiments with embryonic stem cell neurons will provide a unique opportunity to study the integration of neural transplants with normal cells, which is very relevant to possible medical applications of transplants.

描述（由申请人提供）：该项目的目的是创建一个用于研究培养的神经网络的系统，该系统将为观察每个细胞如何与其他细胞连接以及连接性如何变化提供独特的新能力。培养的神经元将在“笼子”中，是塑料结构，可以使过程产生，但要使细胞体紧密接近记录和刺激电极。通过刺激每个神经元并记录所有其他神经的响应，将揭示网络的连通性。该系统将在8 x 8阵列中具有64个笼子，使用光学镊子将64个解离神经元放在笼子中。在单细胞级别详细研究此类网络的能力将远远超出了现在的存在。记录和刺激不会损害神经元，因此随着网络的发展，可以在几周内观察到连通性。将使用定制大规模集成电路上的非常复杂的电子放大器和刺激器，这将以低成本提供同时研究多个笼阵列的能力，而它们在孵化器中。这些研究将为观察正常网络开发的详细信息提供机会，而这些网络开发从来没有可能。此外，将在数小时至几周的时间尺度上揭示对施加模拟网络的影响。药理学对连通性的影响也将是可观察到的。最后，由于它们位于笼子中，因此可以将细胞类型混合并放置在已知位置，因此可以观察到它们在形成网络时之间的类型特异性相互作用。一个最有趣的例子是观察胚胎茎细胞衍生的神经元与正常神经元网络的相互作用。作为本研究结束时概念的证明，将开始此类实验。它们将表明与移植中正常细胞的干细胞神经元整合的潜力，并将为研究如何促进该整合提供机会。公共卫生相关性：研究该项目提供的培养网络的能力将提供有关网络开发，可塑性和药理反应的重要新数据。这将与使用慢性刺激和药物改善神经系统问题的医学应用有关。此外，使用胚胎干细胞神经元的实验将为研究神经移植与正常细胞的整合提供独特的机会，这与移植的可能医疗应用非常相关。