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（由申请人提供）：树突棘和突触的活动和可塑性是正常认知过程（例如学习和记忆）的基础，也是大脑中发现的复杂电路的基础，树突棘是富含肌动蛋白的突起。来自树突轴，包括兴奋性突触的大多数突触后末端，毫不奇怪，树突棘的异常与许多神经系统相关。尽管棘和突触在中枢神经系统中很重要，但调节这些结构的活动和可塑性的分子机制尚不清楚。主要是因为目前缺乏在单个棘/突触水平上探测这些结构的可用技术。此外，研究单个棘和突触的突触活动和可塑性的能力将提供重要的帮助。我们正在开发具有集成石墨烯传感器和电极的新型神经元-胶质细胞共培养微流体装置，并将其与扫描光电流显微镜相结合，以亚突触分辨率（具体）检测和刺激脊柱可塑性。目标我）。 这项技术可以记录单个树突棘和突触的电特性，并检查不同电刺激对这些结构的影响，因为肌动蛋白细胞骨架的重组被认为是树突棘和突触活性、可塑性和功能的基础。探索肌动蛋白结合蛋白 VASP 在调节突触活性和可塑性中的作用（具体目标 II）我们将改变 VASP 的表达并确定其对个体电特性的影响。此外，我们将确定这种蛋白质对突触可塑性的贡献，通过提供强大的技术来研究潜在的机制，这将引起神经生物学家的极大兴趣和益处。单个突触水平上树突棘和突触的电活动和可塑性。