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，是神经功能的直接测量手段。对于科学家来说，记录和刺激清醒行为动物大脑不同区域的神经元数量，将活动与行为联系起来，已经成为一种惯例。然而，同样的电生理学在行为正常的动物的脊髓中表现良好，这是无法克服的。出于这个原因，尽管脊髓是运动和感觉的关键部位，但从功能角度来看，它在很大程度上仍然是一个“黑匣子”，因为缺乏工具来测量和调节脊髓神经元的功能。在行为动物的脊髓中进行电生理学的主要困难是因为脊髓在行为过程中极易移动、移动和弯曲。几乎所有现有的神经电极在机械上都比脊柱组织更坚硬，无法跟随这种运动，因此产生过多的噪音和位置漂移，并导致脊髓损伤或长期惊吓。在这里，我们提出了一套以超柔性电极为中心的技术，以应对社区面临的这一挑战。我们现在有初步数据证明，这些探针可以从行为正常的小鼠的脊髓神经元中获得高质量的单单位记录。值得注意的是，当动物以不同的行为积极移动时，我们仍然能够通过棘波排序稳定地跟踪神经元群体。我们的初步长期结果也证实了植入脊髓后5个月以上的慢性活体记录。在这一成功的激励下，我们提出了优化这项技术用于脊髓研究的研究计划。至关重要的是，我们聚集了一群杰出的神经科学家，与我们一起开发手术方法，并测试不同脊柱区域、动物模型和研究主题的设备。这些努力被组织成三个目标。我们预计，这项新技术将使人们能够以新的视角，在脊髓调节的一系列行为(不同的运动、停止、反射撤退、伸手、抓握、排尿等速度)的背景下，对单个脊髓细胞的功能进行研究。这将使神经科学家能够将发育良好的脊髓细胞类型的遗传和发育特征与回路联系起来；了解神经系统的其他部分如何与脊髓相互作用。从翻译的角度来看，这为通过慢性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；打开了治疗脊髓损伤、中风、运动障碍和运动神经元疾病的脊髓内接口的潜力。