Exploring synaptic remodeling with graphene optoelectronic probes

用石墨烯光电探针探索突触重塑

• 批准号: 9234603
• 负责人: Deyu Li
• 金额: $ 19.39万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9234603
• 关键词: Actin-Binding Protein; Actins; Alzheimer' s Disease; Area; Autistic Disorder; Brain; Carbon; Cell membrane; Cells; Charge; Chemicals; Coculture Techniques; Complex; Cytoskeleton; Data; Dendrites; Dendritic Spines; Development; Devices; Disease; Down Syndrome; Electrodes; Electrons; Epilepsy; Excitatory Synapse; Exploratory/Developmental Grant; Fragile X Syndrome; Individual; Lasers; Lead; Learning; Long-Term Depression; Long-Term Potentiation; Measures; Membrane Potentials; Memory; Mental disorders; Microfluidic Microchips; Microfluidics; Microscopy; Modeling; Molecular; Morphology; Nature; Neuraxis; Neurites; Neuroglia; Neurons; Optics; Pattern; Play; Positioning Attribute; Process; Property; Proteins; Resolution; Role; Scanning; Scheme; Schizophrenia; Site; Spottings; Stimulus; Structure; Surface; Synapses; Synaptic Transmission; Synaptic plasticity; Techniques; Technology; Transistors; Vertebral column; base; cognitive function; cognitive process; density; electrical property; graphene; innovative technologies; insight; interest; monolayer; nervous system disorder; neurotechnology; new technology; novel; novel therapeutic intervention; postsynaptic; public health relevance; response; sensor; single molecule; spatiotemporal; submicron; temporal measurement; vasodilator-stimulated phosphoprotein

 DESCRIPTION (provided by applicant): The activity and plasticity of dendritic spines and synapses underlie normal cognitive processes, such as learning and memory and are the basis for the complex circuitry found in the brain. Dendritic spines, which are actin-rich protrusions that emanate from the dendrite shaft, comprise most postsynaptic terminals of excitatory synapses. Not surprisingly, abnormalities in dendritic spines are associated with a number of neurological disorders, including Fragile-X syndrome, Down's syndrome, Alzheimer's disease, autism, schizophrenia, and epilepsy. Despite the importance of spines and synapses in the central nervous system, the molecular mechanisms that regulate the activity and plasticity of these structures are not well understood largely because of the current lack of available technologies for probing these structures at single spine/synapse levels. Furthermore, the capability to study synaptic activity and plasticity in individual spines and synapses would provide significant insight into the function and molecular mechanisms that regulate these structures. We are developing novel neuron-glia co-culture microfluidic devices with integrated graphene sensors and electrodes and combining them with scanning photocurrent microscopy to detect and stimulate spine plasticity at sub- synaptic resolution (Specific Aim I). We will use this technology to record electrical properties at individual dendritic spines and synapses and to examine the effects of different electrical stimuli on these structures. Since reorganization of te actin cytoskeleton is thought to underlie the activity, plasticity, and function of dendritic spine and synapses, we will explore the role of actin-binding protein VASP in regulating synaptic activity and plasticity (Specific Aim II). We will alter the expression of VASP and determine the effect on the electrical properties of individual dendritic spines and synapses with the graphene probes. Moreover, we will determine the contribution of this protein to synaptic plasticity. The development of the proposed microfluidic platforms will be of great interest and benefit to neurobiologists by providing a powerful technology for investigating the mechanisms that underlie the electrical activity and plasticity of dendritic spines and synapses at a single synaps level.

 描述（由适用提供）：树突状刺和突触的活性和可塑性是正常认知过程的基础，例如学习和记忆，是大脑中复杂电路的基础。树突状棘是富含肌动蛋白的突起，它们从树突轴中散发出来，包括大多数兴奋性突触的突触后末端。毫不奇怪，树突状棘的异常与许多神经系统疾病有关，包括脆弱的X综合征，唐氏综合症，阿尔茨海默氏病，自闭症，精神分裂症和癫痫病。尽管中枢神经系统中刺和突触的重要性，但调节这些结构活性和可塑性的分子机制在很大程度上尚未得到充分了解，因为目前缺乏在单个脊柱/突触水平上探测这些结构的可用技术。此外，研究各个棘突和突触中突触活性和可塑性的能力将提供对调节这些结构的功能和分子机制的重大见解。我们正在开发新型的神经元-GLIA共培养微流体设备，并使用集成的石墨烯传感器和电极与扫描光电流显微镜结合，以检测和刺激亚突触分辨率的脊柱可塑性（特定目标I）。我们将使用 这项技术可记录各个树突状刺和突触的电特性，并检查不同电刺激对这些结构的影响。由于肌动蛋白细胞骨架的重组被认为是树突状脊柱和突触的活性，可塑性和功能的基础，因此我们将探讨肌动蛋白结合蛋白VAS的作用，在确定突触活动和可塑性（特定AIM II）中的作用。我们将改变VASP的表达，并确定对单个树突棘的电特性和与石墨烯问题的突触的影响。此外，我们将确定该蛋白质对突触可塑性的贡献。提出的微流体平台的开发将对神经生物学家产生极大的兴趣和好处，通过提供强大的技术来研究在单个突触水平上树突状刺和突触的电动活动和可塑性的机制。