Optical montoring of modulatory neurotransmitter levels using new infrared nanonsensors

使用新型红外纳米传感器光学监测调节神经递质水平

基本信息

批准号：
9404816
负责人：
Linda E Wilbrecht
金额：
$ 13.84万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9404816
关键词：
Acute Animals Area Attention Axon Behavior Behavioral Binding Biology Brain Calcium Calibration Carbon Cells Corpus striatum structure Cues Data Decision Making Detection Development Disease Dopamine Effectiveness Electrophysiology (science)Extracellular Space Eye Functional Imaging Future Glutamates Goals Grant Gray unit of radiation dose Health Image In Vitro Injection of therapeutic agent Learning Light Measurement Measures Mental Depression Mental disorders Methods Monitor Moods Mus Nanotubes Neocortex Neurobiology Neurosciences Neurotransmitters Norepinephrine Optical Methods Optics Outcome Parkinson Disease Performance Periodicity Pharmaceutical Preparations Pharmacology Play Polymers Preparation Problem Solving Process Property Proteins Psychiatrist Rewards Rodent Role Scanning Schizophrenia Serotonin Signal Transduction Slice Structure Surface Technology Testing Time Translating Vertebral column addiction awake base blind density design experimental study frontal lobe imaging system in vivo in vivo imaging interest mouse model nanoscience nanosensors nervous system disorder neural circuit neuronal cell body neurotransmission optical sensor ratiometric relating to nervous system response sensor single walled carbon nanotube tool

项目摘要

PROJECT SUMMARY Dopamine, norepinephrine, and serotonin are major modulatory neurotransmitters that are implicated in a wide variety of psychiatric and neurological disorders, including addiction. Our available methods to quantify the dynamics of these neurotransmitters in extracellular space are not as fast, sensitive, direct or as clean as we would like. Here we propose to leverage recent progress in nanoscience to solve this problem by moving new near infrared (nIR) nanosensor technology from the nanoscientists' bench into the neurobiologists' rig. For ease of calibration and strong relevance to addiction, we will start with a dopamine nanosensor. We will integrate new nIR nanosensor tools with existing imaging and recording methods in brain slices and intact mice to enable greater understanding of the biology of modulatory neurotransmission. In Specific Aim 1, we plan to develop and calibrate the use of dopamine sensitive nanosensors for ex vivo detection of evoked dopamine release in striatal and frontal cortex brain slices. In Specific Aim 2 we will test the feasibility of using these sensors over long time scales in vivo. In Specific Aim 3, we will image nanosensor response to evoked dopamine release in vivo in intact and potentially awake behaving mice. Our goal is to set the stage to optically monitor dopamine and other neurotransmitter levels in vivo, in response to cues and rewards in conditions which induce reward prediction error in mouse models of health and disease. Development and dissemination of the dopamine nanosensor alone will greatly inform our understanding of substances with abuse potential and the effects of a broad variety of pharmacological agents. Experimental data collected using the dopamine nanosensor will then be applied to facilitate development of the norepinephrine and serotonin sensors. Our ultimate goal is to develop methods for measuring dopamine, norepinephrine, and serotonin in the cortex in vivo simultaneously. New infrared nanosensors have the potential to greatly advance our understanding of the brain, granting us new eyes to see modulatory neurotransmission in real time.

项目概要多巴胺、去甲肾上腺素和血清素是主要的调节神经递质，与广泛的神经递质有关。各种精神和神经疾病，包括成瘾。我们可用的方法来量化这些神经递质在细胞外空间的动态并不像我们那么快速、敏感、直接或干净想。在这里，我们建议利用纳米科学的最新进展，通过移动新的技术来解决这个问题近红外 (nIR) 纳米传感器技术从纳米科学家的工作台转移到神经生物学家的设备中。为了由于易于校准且与成瘾密切相关，我们将从多巴胺纳米传感器开始。我们将将新的近红外纳米传感器工具与脑切片和完整小鼠的现有成像和记录方法相结合以便更好地了解调节神经传递的生物学。在具体目标 1 中，我们计划开发和校准多巴胺敏感纳米传感器的使用，用于体外检测诱发的多巴胺释放在纹状体和额叶皮层脑切片中。在具体目标 2 中，我们将测试使用这些的可行性体内长时间尺度的传感器。在具体目标 3 中，我们将对纳米传感器对诱发的响应进行成像完整且可能清醒的行为小鼠体内多巴胺释放。我们的目标是为光学奠定基础监测体内多巴胺和其他神经递质水平，以响应条件下的提示和奖励这会导致小鼠健康和疾病模型中的奖励预测错误。开发与传播仅多巴胺纳米传感器的研究将极大地帮助我们了解具有滥用潜力的物质以及多种药物的作用。使用多巴胺收集的实验数据然后，纳米传感器将用于促进去甲肾上腺素和血清素传感器的开发。我们的最终目标是开发测量大脑皮层中多巴胺、去甲肾上腺素和血清素的方法体内同时。新型红外纳米传感器有可能极大地增进我们对红外光谱的理解大脑，赋予我们新的眼睛来实时观察调节性神经传递。