Mapping Brain Activity with High Spatiotemporal Resolution using Graphene Probes

使用石墨烯探针以高时空分辨率绘制大脑活动图

• 批准号: 10244939
• 负责人: Deyu Li
• 金额: $ 37.99万
• 依托单位: VANDERBILT 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10244939
• 关键词: Actins; Address; Alzheimer' s Disease; Amacrine Cells; Area; Axon; Behavior; Brain; Brain Mapping; Calcium; Carbon; Categories; Cell membrane; Cell physiology; Cells; Central Nervous System Diseases; Coculture Techniques; Cognitive; Complex; Coupling; Data; Dendrites; Dendritic Spines; Devices; Disease; Down Syndrome; Effectiveness; Electrodes; Electrons; Electrophysiology (science); Environment; Epilepsy; Excitatory Synapse; Exposure to; Fragile X Syndrome; Frequencies; Gases; Glaucoma; Goals; Imaging Techniques; In Situ; In Vitro; Individual; Light; Maintenance; Maps; Measures; Mechanics; Mediating; Membrane; Microelectrodes; Microfluidics; Microscopy; Morphology; Motor; Mus; Myosin ATPase; Nature; Neuraxis; Neurobiology; Neurons; Neurosciences; Neurotransmitters; Optics; Pathologic; Physiological; Population; Property; Proteins; Research; Resolution; Retina; Retinal Ganglion Cells; Sampling; Scanning; Scheme; Schizophrenia; Side; Signal Transduction; Silicon; Site; Slice; Stimulus; Stretching; Structure; Surface; Synapses; System; Technology; Time; Tissues; Transistors; Vertebral column; Visual evoked cortical potential; Wild Type Mouse; autism spectrum disorder; base; biomaterial compatibility; chemokine; design; falls; flexibility; fluorescence imaging; graphene; implantation; in vivo; micromanipulator; millisecond; monolayer; nervous system disorder; neurotechnology; operation; optical imaging; patch clamp; postsynaptic; response; sensor; spatiotemporal; synaptogenesis; temporal measurement; two-dimensional; visual map; voltage; voltage sensitive dye

Project Summary The central nervous system (CNS), the most complex and dynamic network found in nature, is composed of billions of neurons with trillions of dendritic spines and synapses, including pre- and postsynaptic terminals. The postsynaptic side of synapses can take the form of dendritic spines, which are small, actin-rich protrusions that serve as sites of postsynaptic contact and signal integration for most of the excitatory synapses in the CNS. Synapses relay signals between neighboring neurons in large neuronal networks, underscoring their vital function in the CNS. Not surprisingly, abnormalities in dendritic spines/synapses are associated with a number of CNS disorders, including Fragile-X syndrome, Down’s syndrome, Alzheimer’s disease, autism, schizophrenia, and epilepsy, glaucoma, and intellectual disorders. It is, therefore, crucial to understand the relationships between the functional connectivity map of neuronal networks and the physiological or pathological functions of individual synapses and neurons. To address this challenge, we propose to integrate two-dimensional flexible graphene membranes with scanning photocurrent microscopy to probe electrical activities of individual synapses and neurons in the retina and brain, two of the three components of the CNS. A unique advantage of graphene is that its whole volume is exposed to the environment, which maximizes its sensitivity to local electrochemical potential change. For example, graphene transistors are capable of detecting individual gas molecules, due to its high surface-area-to-volume ratio and high electron mobility (100 to 1000 times higher than silicon). The high electron mobility also enables graphene transistors to operate at very high frequencies (up to 500 GHz), leading to high temporal resolution. Because of its strength and flexibility, graphene membranes can adhere to cell membranes or tissue slices to achieve high electrical sensitivity. Furthermore, monolayer graphene transmits more than 97% of incident light, making it ideal to be used as transparent electrical devices that are compatible with optical imaging techniques. In addition, graphene transistors and electrodes have demonstrated the capability of stable operation at stretching up to 9%. As such, we propose to create an unprecedented neurotechnology through a rare combination of flexible graphene transistors and scanning photocurrent microscopy to simultaneously study the electrical activities of a large population of synapses and neurons in vitro, in situ, and in vivo. This technology will allow us to decipher the functional connectivity map of neuronal networks with high spatiotemporal resolution and high throughput.

项目概要 中枢神经系统（CNS）是自然界中最复杂、最动态的网络，由 数十亿个神经元，以及数万亿个树突棘和突触，包括突触前和突触后末梢。 突触的突触后侧可以采取树突棘的形式，它们是富含肌动蛋白的小突起 作为中枢神经系统中大多数兴奋性突触的突触后接触和信号整合的场所。 突触在大型神经元网络中的相邻神经元之间传递信号，强调了它们的重要性 在中枢神经系统中发挥作用。毫不奇怪，树突棘/突触的异常与许多 中枢神经系统疾病，包括脆性 X 综合征、唐氏综合症、阿尔茨海默病、自闭症、精神分裂症、 以及癫痫、青光眼和智力障碍。因此，理解这些关系至关重要 神经元网络的功能连接图与生理或病理功能之间的关系 单个突触和神经元。为了应对这一挑战，我们建议集成二维柔性 石墨烯膜与扫描光电流显微镜探测单个突触的电活动 视网膜和大脑中的神经元，这是中枢神经系统三个组成部分中的两个。石墨烯的独特优势 是它的整个体积暴露在环境中，这最大限度地提高了其对局部电化学的敏感性 潜在的变化。例如，石墨烯晶体管能够检测单个气体分子，这是由于 其高表面积与体积比和高电子迁移率（比硅高 100 至 1000 倍）。高 电子迁移率还使石墨烯晶体管能够在非常高的频率（高达 500 GHz）下运行，领先 达到高时间分辨率。由于其强度和柔韧性，石墨烯膜可以粘附在细胞上 膜或组织切片以实现高电灵敏度。此外，单层石墨烯传输 超过 97% 的入射光，非常适合用作兼容的透明电子器件 与光学成像技术。此外，石墨烯晶体管和电极已经证明了 拉伸至9%时稳定运行的能力。因此，我们建议创建一个前所未有的 通过柔性石墨烯晶体管和扫描光电流的罕见组合的神经技术 显微镜同时研究大量突触和神经元的电活动 体外、原位和体内。这项技术将使我们能够破译神经元的功能连接图 具有高时空分辨率和高吞吐量的网络。

项目成果

Dynamic Observation of Retinal Response to Pressure Elevation in a Microfluidic Chamber.

• DOI: 10.1021/acs.analchem.1c05652
• 发表时间: 2022-09-13
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Esteban-Linares, Alberto;Wareham, Lauren K.;Walmsley, Thayer S.;Holden, Joseph M.;Fitzgerald, Matthew L.;Pan, Zhiliang;Xu, Ya-Qiong;Li, Deyu
• 通讯作者: Li, Deyu