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的关键技术，是神经元功能的直接衡量。科学家在清醒的动物中记录和刺激不同大脑区域的神经元种群已经成为常规，将活动与行为相关联。但是，相同的电生理学在行为动物的脊髓中表现良好，这是无法克服的。因此，尽管脊髓是运动和感觉的关键部位，但由于缺乏在功能上测量和调节脊柱神经元的工具，因此从功能上的角度来看，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因为绳索在行为过程中非常流动，移动和弯曲。几乎所有现有的神经元在机械上比脊柱组织更刚性，都无法跟踪此类运动，因此产生了过度的噪声和位置训练，并长期导致脊柱损伤或恐惧。在这里，我们提出了一套围绕超级电子电子的技术，以应对社区的这一挑战。现在，我们有了初步数据，证明了这些问题从行为小鼠的脊柱神经元中得出了高质量的单个单位记录。明显地，当动物以潜水行为积极移动时，我们仍然能够通过尖峰分类来稳定地跟踪神经元种群。我们的初步长期结果还验证了脊髓中植入后5个月以上的慢性记录。在这一成功的推动下，我们提出了研究计划，以优化脊髓研究的这项技术。至关重要的是，我们将一群杰出的神经科学家召集在一起，与我们一起开发外科手术方法，并在不同的脊柱区域，动物模型和研究主题上测试设备。这些努力分为三个目标。我们希望这项新技术将在脊髓介导的广泛行为的背景下对单个脊柱细胞的功能进行新的观点（不同的运动速度，停止，反射撤回，伸手可及，握住，握住，排尿等）。这将使神经科学家能够将脊柱细胞类型的发达遗传和发育表征连接到电路。了解神经系统的其他部位如何与脊髓相互作用。从转化的角度来看，这为通过长期监测更好地理解脊髓损伤和疾病的病因和进展提供了机会。打开治疗脊髓损伤，中风，运动障碍和运动神经元疾病的脊柱内界面的潜力。