Single neuronal recordings using movable mircrophobes

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。该提案的总体目标是开发一种可靠的技术，用于记录慢性实验中单个神经元的电位。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致动器和相关的微电极技术，以实现微电极植入后的重新定位。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。在本提案中，开发该技术的关键目标是(a)实现高质量、可靠的单单元电记录，即使是在清醒、行为的啮齿动物的大脑深层结构中，也能实现神经元群的高质量、可靠的单单元电记录；(b)在急性和长期实验中实现微电极的可靠定位和重新定位；(c)评估微电极运动对周围脑组织的影响。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。除了在我们自己对中风损伤和恢复的神经元机制的研究中带来新的发现外，这项新技术将立即影响到我们合作者的几个NIH资助的赠款。微致动微电极将在一个场景中进行测试，该场景需要从大脑深部核的神经元中进行准确的长期记录。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 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.