Single neuronal recordings using movable mircrophobes

描述（由申请人提供）： 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，迄今为止已经开发了许多这样的设备。 然而，目前用于监测体内单个神经元功能的植入式微电极技术在慢性情况下通常失败，这可能是由于定位机制中的机械漂移、脑组织的微动和植入部位周围的神经胶质增生。 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。 我们建议开发一种新型的微制造热微致动器和相关的微电极技术与桑迪亚国家实验室合作，使植入后的微电极重新定位。 使用微致动器在植入后重新定位微电极的灵活性（在故障或其他情况下）将潜在地增加在清醒和行为动物的慢性实验中体内单神经元记录的可靠性和一致性。 在该提议中开发该技术的关键目标是（a）实现来自神经元集合的高质量、可靠的单个单元电记录，甚至在清醒的行为啮齿动物的大脑深层结构中（B），以实现在急性和长期实验中微电极的可靠定位和重新定位，以及（c）评估微电极运动对周围脑组织的影响。 我们将使用建模和仿真，新颖的微加工和封装技术，台式测试和体内测试方法的设计，表征和验证相结合。 除了在我们自己对中风损伤和恢复的神经元机制的研究中有新的发现外，这项新技术还将立即影响我们合作者的几项NIH资助的赠款。 微驱动微电极将在需要从大脑深层核团的神经元进行准确长期记录的情况下进行测试。 将在合作者的帮助下确保独立评估和传播，这些合作者进行体内实验，以了解记忆提取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.