Single neuronal recordings using movable mircroprobes

描述（由申请人提供）：神经科学家很早就认识到使用微电极阵列来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经常失败，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形成。这个竞争性修订的总体目标（通知编号no - od -09-058和通知标题：NIH宣布竞争性修订应用的恢复法案基金的可用性）是开发一种可靠的技术，用于记录慢性实验中单个神经元和神经元网络集合的电位。我们的母基金专注于与桑迪亚国家实验室合作开发一种新型微制造热微致动器和相关的微电极技术，以实现植入后微电极的重新定位。使用微致动器在植入后（在失败或其他情况下）重新定位微电极的灵活性，将潜在地增加在清醒和行为正常的动物体内进行的慢性实验中单神经元记录的可靠性和一致性。这项竞争性修订将与4年期父母补助金的最后两年同时进行。这项为期2年的工作的具体目标是(a)设计，开发和测试两种新的核心技术，用于创建具有移动机械部件的3D微芯片堆栈，这将使我们能够构建独立可移动微电极的3D集群；b)在慢性啮齿动物实验中验证最优的3D可移动微电极集群。我们将结合建模和仿真、新型微加工和封装技术、台式测试和体内测试方法进行设计、表征和验证。除了在我们自己对神经元可塑性机制的研究中带来新发现外，这项新技术将立即影响到我们合作者的几项NIH资助的资助。在研究记忆的提取与巩固机制、衰老、听觉生理、皮质修复等方面的记忆缺陷等方面，通过研究人员的体内实验，保证研究成果的独立评价与传播。

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 this competitive revision (Notice Number NOT-OD-09-058 and Notice Title: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications) is to develop a reliable technology for recording electrical potentials from ensembles of single neurons and neuronal networks in chronic experiments. Our parent grant is focused on developing 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. This competitive revision will run concurrently with the last two years of the 4 year parent grant. The specific aims of this proposed 2-year effort are (a) to design, develop and test two novel core technologies for creating 3D stacks of microchips with moving mechanical parts that will allow us to build a 3D cluster of independently movable microelectrodes and b) to validate the most optimal 3D cluster of movable microelectrodes in chronic rodent experiments. 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 plasticity, this new technology will immediately impact several NIH funded grants of our collaborators. 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. PUBLIC HEALTH RELEVANCE: Successful completion of the proposed project will result in the development of a novel technology that will allow us to reliably and consistently monitor the activity of individual neurons in the brain. Current technologies fail in long-term experiments and clinical situations. The proposed technology will therefore have a significant impact in improving the success of emerging brain prostheses technologies besides facilitating key discoveries in long-term Neurophysiological events.