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

可与中枢神经系统无缝集成的注射器注射网状电子器件

• 批准号: 9341423
• 负责人: CHARLES M LIEBER
• 金额: $ 118.3万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9341423
• 关键词: Aging; Alzheimer' s Disease; Area; Behavior; Biological Neural Networks; Brain; Brain region; Cells; Chronic; Cognitive; Complex; Development; Devices; Disease; Electrodes; Electronics; Eye; Goals; Healthcare; Immune response; Impaired cognition; Impairment; Implant; Injectable; Injection of therapeutic agent; Label; Learning; Longitudinal Studies; Maps; Memory; Methods; Mus; Nervous system structure; Neuraxis; Neurodegenerative Disorders; Neurons; Positioning Attribute; Resolution; Retina; Retinal; Rodent; Science; Spinal Cord; Spinal cord injury; Structure; Syringes; System; Therapeutic; Tissues; Traumatic injury; awake; design; imaging study; in vivo; insight; intravitreal injection; mechanical properties; minimally invasive; motor control; motor disorder; nervous system disorder; neural circuit; neural prosthesis; neurodevelopment; novel; novel strategies; novel therapeutic intervention; relating to nervous system; spine bone structure; tool; visual stimulus

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.

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，如果满足，它将提供 对大脑功能的批判性洞察力，可以为发展神经系统疾病的治疗和 疾病。在这方面，在几个月内用细胞分辨率绘制和调节相同神经网络的能力 例如，多年对于阐明现有神经元如何演变成具有多种动态的神经回路至关重要 通过学习或了解与神经退行性引起的与衰老相关的大脑变化和认知下降 疾病。该项目将探索一个新的范式，用于将电子在大脑中无缝整合，称为注射器 - 可注射的网格电子设备，以提供这些密钥映射和调制功能。这种方法以 开发具有大小，连通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，这些神经元通过受控注射器注射以形成稳定的非侵入性 中枢神经系统中的植入物。将进行系统的纵向研究，以跟踪神经活动 与运动控制功能障碍或功能障碍相关的多个大脑区域之间的单神经元分辨率， 与衰老和阿尔茨海默氏病有关的记忆和认知能力。网格电子探针将被注入 定义相关电路的啮齿动物的不同大脑区域，并进行了成像研究以表征 神经网络/网格电子结构。神经活动的长期记录和分析将用于照明 与老化以及阿尔茨海默氏病有关的电路行为。刺激器电极也将集成 网格电子探测器，将用于调节活动，这将提供进一步的了解 复杂的系统级电路，并指向潜在的治疗应用。另外，注射器注射网格 电子产品将用于研究神经系统其他部位的研究，包括视网膜和脊髓，其中 很难实施更常规的刚性探针。玻璃体内注射将用于输送网格 电子产品以微创的方式到小鼠的杯状视网膜。小鼠视网膜的慢性体内研究将 进行以优化网格设计以进行映射，以定义针对网格电极的位置 荧光标记的视网膜细胞，并在醒着的约束小鼠处记录不同的视网膜细胞 不同的视觉刺激。最后，注射注射器可注射的网格电子设备将以新的方法整合电气 开发神经假体治疗脊髓损伤的探针。网状电子将被注入 在啮齿动物中的椎骨之间，用于研究感应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，最终的目的是开发新的治疗方法 脊髓损伤。