Optimizing ultraflexible electrodes and integrated electronics for high-resolution, large-scale intraspinal recording and modulation

优化超柔性电极和集成电子器件以实现高分辨率、大规模椎管内记录和调制

• 批准号: 10617092
• 负责人: Lan Luan
• 金额: $ 163.27万
• 依托单位: RICE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617092
• 关键词: Address; Animal Experimentation; Animal Model; Animals; Area; Behavior; Bilateral; Brain; Brain region; Cells; Characteristics; Chronic; Cicatrix; Communities; Computer software; Computers; Data; Destinations; Development; Devices; Diameter; Disease; Electrodes; Electronics; Electrophysiology (science); Esthesia; Etiology; Future; Genetic; Individual; Laboratories; Locomotion; Measures; Mechanics; Mediating; Mission; Monitor; Motor Neuron Disease; Movement; Movement Disorders; Mus; Nervous System; Neurologic; Neurons; Neurosciences; Noise; Operative Surgical Procedures; Population; Positioning Attribute; Protocols documentation; Public Health; Rattus; Reflex action; Research; Resolution; Rice; Rodent; Scientist; Sensory; Site; Sorting; Speed; Spinal; Spinal Cord; Spinal Injuries; Spinal cord injury; Stroke; Structure; System; Techniques; Technology; Testing; Tissues; United States National Institutes of Health; Urination; Vertebral column; Weight; Withdrawal; Work; awake; brain tissue; cell type; data streams; density; design; digital; disorder prevention; flexibility; grasp; implantation; improved; in vivo; light weight; meter; miniaturize; nanoelectronics; neural; neural circuit; neuromechanism; new technology; pilot test; response; scale up; success; tool

Electrophysiology is a critical technology in neuroscience as a direct measure of neuronal functions. It has become routine for scientists to record and stimulate neuron populations in different brain regions in awake behaving animals, correlating activity with behavior. However, it has been insurmountable for the same electrophysiology to perform well in the spinal cord of behaving animals. For this reason, while the spinal cord is a critical site for locomotion and sensations, it remains largely a “black box” from a functional perspective, due to the lack of tools to measure and modulate spinal neurons while they are functioning. The main difficulty of doing electrophysiology in the spinal cord of behaving animals is because the cord is extremely mobile, moving and bending during behavior. Almost all existing neural electrodes, being mechanically more rigid than spinal tissues, fail to follow such movements, therefore yielding excessive noise and position drifts and lead to spinal injury or scaring in the long term. Here, we propose a suite of technologies centering around ultraflexible electrodes to address this challenge for the community. We now have preliminary data proving these probes achieved high quality single unit recording from spinal neurons of behaving mice. Markedly, when the animals are actively moving in diverse behaviors, we were still able to stably track neuron populations through spike sorting. Our preliminary long-term results also verified chronic in vivo recording for over 5 months after implantation in the spinal cord. Motivated by this success, we propose research plans to optimize this technology for spinal cord studies. Critically, we have brought together a group of outstanding neuroscientists to work with us in developing surgical approaches, and testing devices across different spinal areas, animal models, and research topics. These efforts are organized into three aims. We expect this new technology will enable new perspectives on the function of individual spinal cells in the context of a wide spectrum of behaviors that the spinal cord mediates (different speeds of locomotion, stopping, reflex withdrawal, reaching, grasping, urination, etc.). This will allow neuroscientists to connect the well-developed genetic and developmental characterization of spinal cell types to the circuit; to understand how other parts of the nervous system interact with the spinal cord. From a translational perspective, this offers the opportunity for a better understanding of the etiology and progression of spinal cord injury and disease by chronic monitoring; opens up the potential for intra-spinal interfaces that treat spinal cord injury, stroke, movement disorders, and motor neuron diseases.

电生理学是神经科学中的一项关键技术，可以直接测量神经功能，记录和刺激清醒行为动物的不同大脑区域的神经元群，将活动与行为联系起来，这已成为科学家的常规技术。因此，虽然脊髓是运动和感觉的关键部位，但由于缺乏测量工具，从功能角度来看，它在很大程度上仍然是一个“黑匣子”。在行为动物的脊髓中进行电生理学的主要困难是，几乎所有现有的神经电极在机械上都比脊髓组织更坚硬，因此在行为过程中会移动和弯曲。无法跟随这样的运动，因此会产生过多的噪音和位置漂移，并导致长期的脊柱损伤或恐惧。在这里，我们提出了一套以超柔性电极为中心的技术来解决社区的这一挑战。证明这些探针从行为小鼠的脊髓神经元中实现了高质量的单单位记录。值得注意的是，当动物以不同的行为活动时，我们仍然能够通过尖峰分类稳定地跟踪神经元群体。在植入脊髓后 5 个多月的时间里，我们提出了优化这项技术以用于脊髓研究的研究计划，重要的是，我们聚集了一群杰出的神经科学家与我们合作开发手术方法，并且跨不同的测试设备我们预计这项新技术将在脊髓介导的广泛行为（不同的行为）的背景下为单个脊髓细胞的功能提供新的视角。运动、停止、反射撤回、伸手、抓握、排尿等的速度）这将使神经科学家能够将脊髓细胞类型的成熟遗传和发育特征与回路联系起来，以了解神经系统的其他部分是如何工作的；与脊髓相互作用。从转化的角度来看，这为通过长期监测更好地了解脊髓损伤和疾病的病因和进展提供了机会，开辟了治疗脊髓损伤、中风、运动障碍和运动神经元的脊髓内接口的潜力；疾病。