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

项目摘要/摘要： 了解哺乳动物大脑中的复杂电路仍然是一个重大挑战，如果得到满足，将提供 对大脑功能的关键洞察，并可为开发神经疾病的治疗方法和 疾病。在这方面，在几个月内以细胞分辨率映射和调制相同的神经网络的能力 例如，对于阐明现有神经元如何进化为具有不同动力学的神经回路，几年将是至关重要的。 通过学习，了解衰老引起的脑变化和认知功能减退所致的神经退行性改变 疾病。这个项目将探索一种将电子设备无缝集成到大脑中的新范例，称为注射器- 可注入网状电子产品，以提供这些关键的映射和调制功能。这种方法的中心是 具有尺寸、连通性和机械性能的记录和刺激电极网络的发展 类似于神经元和神经组织，通过受控注射器注射形成稳定的非侵入性 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 与运动控制障碍或功能障碍相关的多个脑区的单个神经元分辨率， 记忆和认知能力与衰老和阿尔茨海默病有关。网状电子探头将被注入 啮齿类动物定义相关回路的不同大脑区域，以及为表征 神经网络/网状电子结构。神经活动的长期记录和分析将用于阐明 与衰老和阿尔茨海默病相关的电路行为。刺激器电极也将集成在 网状电子探头将被用来调节活动，这将提供对 复杂的系统级电路，并指出潜在的治疗应用。此外，注射器可注射的网眼 电子学将被开发用于研究神经系统的其他区域，包括视网膜和脊髓，在那里 很难实现更传统的刚性探头。将使用非轴向玻璃体内注射来输送网状物 以一种微创的方式将电子设备连接到小鼠的杯状视网膜。小鼠视网膜的慢性体内研究 对视网膜前展开的网眼设计进行优化，以确定网眼电极相对于 荧光标记的视网膜细胞，并从不同的视网膜细胞记录当清醒的小鼠受到 不同的视觉刺激。最后，注射器可注射的网状电子设备将被用于集成电子设备 脊髓损伤治疗用神经假体的发展探讨。网状电子设备将被注入 并用于研究感觉电极和刺激电极与脊髓的接口 在有无脊髓损伤的情况下，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.