Mapping Brain Activity with High Spatiotemporal Resolution using Graphene Probes

项目摘要 中枢神经系统（CNS）是自然界中最复杂和动态的网络， 由数十亿个神经元组成，有数万亿个树突棘和突触，包括突触前和突触后的末端。 突触的突触后侧可以采取树突棘的形式，树突棘是小的、富含肌动蛋白的突起 其作为CNS中大多数兴奋性突触的突触后接触和信号整合的位点。 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CNS中发挥作用。毫不奇怪，树突棘/突触的异常与一些 中枢神经系统疾病，包括脆性X综合征，唐氏综合征，阿尔茨海默病，自闭症，精神分裂症， 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神经元网络的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，我们建议将二维柔性 石墨烯膜与扫描光电流显微镜探测单个突触的电活动 以及视网膜和大脑中的神经元，它们是中枢神经系统的三个组成部分中的两个。石墨烯的独特优势 它的整个体积都暴露在环境中，这使它对局部电化学的敏感性最大化。 潜在的变化。例如，石墨烯晶体管能够检测单独的气体分子，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）下工作， 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，使其非常适合用作兼容的透明电气设备 光学成像技术。此外，石墨烯晶体管和电极已经证明了 拉伸率达9%时能稳定工作。因此，我们建议建立一个前所未有的 通过柔性石墨烯晶体管和扫描光电流的罕见组合， 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。

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.