Single neuronal recordings using movable mircrophobes

描述(申请人提供)：神经科学家早就认识到使用微电极阵列记录神经元群体的细胞外电位的重要性，到目前为止已经开发了许多这样的设备。然而，目前用于在体内监测单个神经元功能的植入式微电极技术在慢性情况下往往失败，可能是由于定位机制的机械漂移、脑组织的微运动和植入部位周围的胶质细胞增生。该提案的总体目标是开发一种可靠的技术，用于在慢性实验中记录单个神经元的电位。我们建议与桑迪亚国家实验室合作开发一种新型的微制造热微执行器和相关的微电极技术，以便能够在植入后重新定位微电极。在植入后(在故障或其他情况下)使用微执行器重新定位微电极的灵活性，可能会在清醒和行为正常的动物的慢性实验中增加体内单个神经元记录的可靠性和一致性。在这项提议中开发这项技术的主要目标是：(A)实现高质量、可靠的单位电记录，即使在清醒状态下表现为啮齿动物的大脑深层结构中也是如此；(B)能够在急性和长期实验中可靠地定位和重新定位微电极；以及(C)评估微电极移动对周围脑组织的影响。我们将使用建模和模拟、新颖的微制造和封装技术、台式测试和体内测试相结合的方法进行设计、表征和验证。除了在我们自己对中风损伤和康复的神经机制的研究中取得新的发现外，这项新技术还将立即影响我们合作者的几笔由NIH资助的赠款。微驱动微电极将在需要从大脑深层核团中的神经元进行准确的长期记录的情况下进行测试。将确保独立的评估和传播，通过合作者进行活体实验，了解记忆恢复和巩固的机制，以及衰老、听觉生理学、皮质假体等方面的记忆缺陷。

DESCRIPTION (provided by applicant): Neuroscientists have long recognized the significance of using microelectrode arrays for recording extracellular potentials from populations of neurons, for which a number of such devices have been developed so far. However, current implantable microelectrode technologies to monitor single neuronal function in-vivo often fail in chronic situations, likely due to mechanical drift in positioning mechanisms, micromotion of brain tissue and gliosis around the implant site. The overall goal of the proposal is to develop a reliable technology for recording electrical potentials from single neurons in chronic experiments. We propose to develop a novel microfabricated thermal microactuator and associated microelectrode technology in collaboration with Sandia National Laboratories to enable repositioning of microelectrodes after implantation. The flexibility to reposition the microelectrodes after implantation (in the event of a failure or otherwise) using microactuators will potentially increase the reliability and consistency of single-neuronal recordings in-vivo in chronic experiments with awake and behaving animals. The key goals for developing this technology in this proposal are (a) to enable high quality, reliable single- unit electrical recordings from ensembles of neurons even in deep structures of the brain in awake, behaving rodents (b) to enable reliable positioning and repositioning of microelectrodes in both acute and long-term experiments and (c) assess the effect of microelectrode movement on the surrounding brain tissue. We will use a combination of modeling and simulation, novel microfabrication and packaging techniques, bench-top testing and in-vivo testing approaches for design, characterization and validation. Besides leading to novel discoveries in our own research into neuronal mechanisms of stroke injury and recovery, this new technology will immediately impact several NIH funded grants of our collaborators. The microactuated microelectrode will be tested in a scenario that demands accurate long-term recording from neurons in deep nuclei of the brain. Independent evaluation and dissemination will be ensured with the help of collaborators doing in vivo experiments for understanding the mechanisms of memory retrieval and consolidation and memory deficits in aging, auditory physiology, cortical prostheses etc.