Study Exocytosis in the Region of Synaptic Cleft using Electrochemical Nanoprobe

使用电化学纳米探针研究突触间隙区域的胞吐作用

基本信息

批准号：
8723916
负责人：
Mei Shen
金额：
$ 15.7万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8723916
关键词：
3-Dimensional Acetylcholine Action Potentials Aging Alzheimer&apos s Disease Animal Model Aplysia Basic Science Biological Biology Blood capillaries Brain Cell Communication Cells Chemicals Communities Coupled Defect Detection Development Disease Dopamine Drug abuse Electrochemistry Electrodes Electrolytes Electron Transport Exocytosis Extracellular Space Glean Goals Heterogeneity Hormones Image Ions Knowledge Lasers Lead Measurement Measures Medicine Memory Loss Methods Microelectrodes Microscope Microscopy Modeling Nanotechnology Nerve Degeneration Nervous system structure Neurons Neurosciences Neurotransmitters Noise Outcome Parkinson Disease Positioning Attribute Process Quartz Radial Research Resolution Scanning Scanning Electron Microscopy Serotonin Signal Transduction Solutions Stimulus Synapses Synaptic Cleft System Techniques Technology Time Water analytical tool base capillary drug of abuse experience improved innovation insight instrument nano nanometer nanoprobe nanoscale nanoscience nanosensors nervous system disorder neurochemistry neuropathology neurotransmission neurotransmitter release neurotransmitter uptake novel public health relevance sensor simulation technology development

项目摘要

DESCRIPTION (provided by applicant): Vesicular release of neurotransmitters, the process of exocytosis, impacts many functional aspects of the nervous system. Changes in neurotransmitter release are implicated in drug abuse, diseases (e.g. Parkinson's, Alzheimer's), aging and memory loss. Significant progress has been made in understanding exocytosis via electrochemical studies of neurotransmitters via microelectrodes. However, current techniques are limited to a spatial resolution of approximately a micron, making it difficult to study neurotransmitter dynamics near and within the synapse. In order to study exocytosis with significantly improved spatial resolution recording and measurement, methods and instruments with nanometer resolution are needed. In addition, it has been difficult to study non-electrochemically active neurotransmitters (e.g., acetylcholine) using traditional sensors. Here we propose to develop electrochemical sensor that will enable us to interrogate exocytosis with a nanometer resolution. A key objective is qualitative and quantitative measurement of neurotransmitter release and uptake within model synapses of Aplysia californica neurons with both appropriate electrical (action potentials) and chemical stimuli (e.g. K+, Ca2+). The novel nanosensor allows the detection of both electrochemical active and non-active neurotransmitters. Our armamentarium includes novel nanopositioning, imaging and measurement systems based on scanning electrochemical microscope. These tightly coupled technology development and neuroscience efforts will resolve issues related to neurotransmitter identity, concentration, and the conditions needed for transmitter release with nanometer spatial resolution, improved signal to noise ratio, and high temporal resolution. These efforts are well matched to the goal of PA-11-149, "Nanoscience and Nanotechnology in Biology and Medicine." The approaches are general and adaptable to a range of neuronal cells. The resulting new toolset and new knowledge about neurotransmission will be transferrable to broader research community and will have a high impact on the neurochemical research.

描述（由申请人提供）：神经递质的囊泡释放（胞吐作用过程）影响神经系统的许多功能方面。神经递质释放的变化与药物滥用、疾病（例如帕金森病、阿尔茨海默病）、衰老和记忆丧失有关。通过微电极对神经递质进行电化学研究，在理解胞吐作用方面取得了重大进展。然而，当前的技术仅限于大约一微米的空间分辨率，使得研究突触附近和突触内的神经递质动力学变得困难。为了通过显着提高空间分辨率记录和测量来研究胞吐作用，需要具有纳米分辨率的方法和仪器。此外，使用传统传感器研究非电化学活性神经递质（例如乙酰胆碱）也很困难。在这里，我们建议开发电化学传感器，使我们能够以纳米分辨率询问胞吐作用。一个关键目标是在适当的电（动作电位）和化学刺激（例如 K+、Ca2+）下，定性和定量测量加州海兔神经元模型突触内神经递质的释放和摄取。这种新型纳米传感器可以检测电化学活性和非活性神经递质。我们的装备包括基于扫描电化学显微镜的新型纳米定位、成像和测量系统。这些紧密结合的技术开发和神经科学工作将解决与神经递质特性、浓度以及以纳米空间分辨率、改进的信噪比和高时间分辨率释放递质所需的条件相关的问题。这些努力与 PA-11-149“生物和医学中的纳米科学和纳米技术”的目标非常吻合。这些方法是通用的并且适用于一系列神经元细胞。由此产生的新工具集和有关神经传递的新知识将可转移到更广泛的研究界，并对神经化学研究产生重大影响。