Syringe-Injectable Mesh Electronics for Seamless Integration with the Central Nervous System

项目概要/摘要： 了解哺乳动物大脑内的复杂电路仍然是一个重大挑战，如果能够实现， 对大脑功能的重要见解，可以为开发神经系统疾病的治疗方法提供指导， 疾病在这方面，在数月内以细胞分辨率映射和调节相同神经网络的能力， 例如，要阐明现有的神经元如何进化成具有不同动力学的神经回路， 通过学习，或了解与衰老相关的大脑变化和神经退行性疾病引起的认知能力下降 疾病这个项目将探索一种新的模式，无缝集成电子在大脑中，称为注射器， 可注入的网状电子器件，以提供这些关键的映射和调制能力。这种方法的核心是 开发具有尺寸、连接性和机械性能的记录和刺激电极网络 类似于神经元和神经组织，其通过受控的注射器注射递送以形成稳定的非侵入性的 植入中枢神经系统将进行系统的纵向研究，以跟踪神经活动， 与运动控制损伤或功能障碍相关的多个脑区的单神经元分辨率， 记忆和认知能力与衰老和阿尔茨海默病有关。将网状电子探针注入 啮齿动物的不同大脑区域定义了相关的电路，并进行了成像研究，以表征 神经网络/网状电子结构。对神经活动的长期记录和分析将被用来阐明 与衰老以及阿尔茨海默病相关的电路行为。刺激器电极也将集成在 网状电子探测器将用于调节活性，这将进一步了解 复杂的系统级电路，并指出潜在的治疗应用。此外，可注射的网状物 电子学将被开发用于神经系统的其他领域的研究，包括视网膜和脊髓， 难以实现更传统的刚性探针。将使用非轴向玻璃体内注射输送补片 将电子设备以微创方式植入小鼠的杯状视网膜。小鼠视网膜的慢性体内研究将 以优化用于视网膜前展开的网格设计，以限定网格电极相对于 荧光标记的视网膜细胞，并记录当清醒的受限制小鼠经受 不同的视觉刺激最后，可注入的网状电子器件将用于一种新的方法来集成电气 开发用于治疗脊髓损伤的神经修复术的探针。网状电子设备将被注入 并用于研究传感和刺激电极与脊髓的接口 在存在和不存在脊髓损伤的情况下，最终目标是开发新的治疗方法， 脊髓损伤

Project Summary/Abstract: Understanding the complex circuitry within mammalian brains remains a major challenge, which, if met, will provide critical insight into brain function and could provide guidance for developing treatments of neurological disorders and diseases. In this regard, the ability to map and modulate the same neural network with cellular resolution over months to years would be vital for elucidating, for example, how existing neurons evolve into neural circuits with diverse dynamics through learning, or to understand aging-associated brain changes and cognitive decline caused by neurodegenerative diseases. This project will explore a new paradigm for seamlessly integrating electronics within the brain, termed syringe- injectable mesh electronics, to provide these key mapping and modulation capabilities. This approach centers on the development of networks of recording and stimulating electrodes with size, connectivity and mechanical properties similar to neurons and neural tissue, which are delivered by controlled syringe injection to form stable non-invasive implants within the central nervous system. Systematic longitudinal studies will be carried out to track neural activity with single-neuron resolution across multiple brain regions associated with impairment or dysfunction of motor control, memory and cognitive capability related to aging and Alzheimer's disease. Mesh electronic probes will be injected into the distinct brain regions of rodents that define relevant circuitry, and imaging studies carried out to characterize the neural network/mesh electronics structures. Long-term recording and analysis of neural activity will be used to illuminate circuit behavior associated with aging as well as Alzheimer's disease. Stimulator electrodes will also be integrated within the mesh electronics probes and will be used to modulate activity, which will provide further understanding of the complex system-level circuitry and point to potential therapeutic applications. In addition, the syringe-injectable mesh electronics will be developed for studies of other areas of the nervous system, including the retina and spinal cord, where it is difficult to implement more conventional rigid probes. Non-axial intravitreal injection will be used to deliver mesh electronics to the cup-like retina of mice in a minimally invasive manner. Chronic in-vivo studies of the mouse retina will be carried out to optimize mesh design for epiretinal unfolding, to define positions of the mesh electrodes with respect to fluorescently labeled retinal cells, and to record from different retinal cells when awake restrained mice are subjected to different visual stimuli. Last, syringe-injectable mesh electronics will be used in a new approach to integrate electrical probes for development of neural prosthetics for treatment of spinal cord injury. The mesh electronics will be injected between vertebrae in rodents and used to investigate interfacing of sensing and stimulation electrodes with the spinal cord in the presence and absence of spinal cord injury, with the ultimate goal of developing new therapeutic approaches for spinal cord injury.