Optical Nanosensors Detect Neurotransmitter Release in the Peripheral Nervous System

光学纳米传感器检测周围神经系统中神经递质的释放

基本信息

批准号：
10003578
负责人：
Heather A Clark
金额：
$ 63.12万
依托单位：
NORTHEASTERN UNIVERSITY
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：
2017-09-22 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10003578
关键词：
Acetylcholine Adolescent Age Ambystoma Anatomy Animal Model Animals Biological Biology Brain Brain Mapping CRISPR/Cas technology Chemicals Communication Communities Complex Coupled DNA Dendrimers Detection Development Diffuse Disease Drug Kinetics Electrodes Environment Enzymes Feedback Fluorescence Fluorescence Microscopy Genetic Genetic Engineering Genetically Engineered Mouse Guide RNA Image Immune Immune response Immune signaling Immune system Inflammation Light Maps Measures Methodology Microdialysis Modeling Modification Molecular Monitor Natural regeneration Nerve Nervous system structure Neurons Neurosecretory Systems Neurotransmitters Optics Organ Outcome Pathway interactions Penetration Peripheral Peripheral Nervous System Physiological Play Prosthesis Reflex action Role Salamander Signal Transduction Spleen System Tail Techniques Technology Tissues Transgenic Model Translating Translations Vagus nerve structure base biomaterial compatibility cellular imaging cholinergic cholinergic neuron fluorescence imaging imaging agent imaging probe in vivo in vivo imaging interest limb regeneration nanoscale nanosensors neural circuit neurophysiology neurotransmitter release novel strategies nuclease optogenetics prevent regenerative relating to nervous system response to injury scaffold sensor single molecule tissue phantom tool vagus nerve stimulation

项目摘要

ABSTRACT Recent converging evidence suggests that communication between the immune system and the brain is critical for controlling inflammation. The brain receives information in response to injury induced inflammation in the periphery which in turn initiates a reflex mechanism to suppress immune responses. The resulting neuroendocrine reflex plays an important regulatory role in the immune system. These bidirectional brain-peripheral immune communications operate reflexively, in a closed feedback loop whereby neural circuits can exert significant influence to modulate inflammation. However, the specific mechanisms underlying this brain-immune signaling are largely unknown. Therefore, understanding the distinct molecular and neurophysiological mechanisms that govern these complex pathways is critical, which motivates us to develop new approaches to accurately detect and monitor these changes. We will develop nanosensors for the detection of neurotransmitter release in the peripheral nervous system of axolotls (regenerating salamanders). Our nanosensors are based on a modular platform that can easily be tuned to an appropriate dynamic range, wavelengths for tissue penetration, and size to be compatible with the in vivo environment. The juvenile axolotl is highly transparent and nanosensors injected into the nervous system or organs will be imaged using light sheet fluorescence microscopy. In addition, we have the ability to genetically modify the system to develop a transgenic model that can be stimulated with light to target neuronal excitations, while simultaneously measuring neurotransmitter levels via the fluorescence emitted from the injected nanosensors. Combined, we will image volumetric release of acetylcholine in the peripheral nervous system and spleen of the axolotl, and will translate these results to a mammalian model by the end of the project period.

抽象的最近的融合证据表明，免疫系统与大脑对于控制炎症至关重要。大脑收到响应伤害的信息诱导的外围炎症又启动了反射机制以抑制免疫反应。由此产生的神经内分泌反射在免疫系统。这些双向脑外围免疫通信运作反射性地，在封闭的反馈回路中，神经回路可以对调节炎症。但是，这种脑免疫的具体机制信号传导在很大程度上未知。因此，了解独特的分子和控制这些复杂途径的神经生理机制至关重要，这激发了我们开发新方法来准确检测和监视这些变化。我们将发展用于检测神经递质释放的纳米传感器 Axolotls（再生sal）。我们的纳米传感器基于一个模块化平台可以轻松调节适当的动态范围，用于组织穿透的波长，以及大小与体内环境兼容。少年axolotl高度透明，并且注入神经系统或器官的纳米传感器将使用轻片成像荧光显微镜。另外，我们有能力将系统修改为开发一个可以用光刺激以靶向神经元激发的转基因模型，而通过注射的荧光同时测量神经递质水平纳米传感器。合并，我们将图像乙酰胆碱在周围的体积释放神经系统和Axolotl的脾脏，并将这些结果转化为哺乳动物模型到项目期结束时。