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

• 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
• 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

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.

摘要 最近越来越多的证据表明，免疫系统和 大脑对控制炎症至关重要。大脑接受对损伤作出反应的信息。 诱导外周炎症，进而启动反射机制以抑制 免疫反应。由此产生的神经内分泌反射在 免疫系统。这些双向的大脑-外周免疫通讯运作 反射性地，在闭合反馈环路中，神经电路可以对 调节炎症。然而，这种大脑免疫的具体机制 信号在很大程度上是未知的。因此，理解不同的分子和 支配这些复杂通路的神经生理机制至关重要，这促使 我们需要开发新的方法来准确地检测和监测这些变化。我们将发展 应用纳米传感器检测小鼠外周神经系统神经递质释放 Axolotls(再生火蜥蜴)。我们的纳米传感器基于模块化平台， 可以很容易地调整到适当的动态范围，用于组织渗透的波长，以及 尺寸与体内环境兼容。幼年紫杉醇的透明度很高， 注射到神经系统或器官中的纳米传感器将使用光片成像 荧光显微镜。此外，我们有能力对系统进行基因改造，以 开发一种转基因模型，可以用光刺激来靶向神经元兴奋，而 通过注射后发出的荧光同时测量神经递质水平 纳米传感器。结合起来，我们将成像乙酰胆碱在外周的体积释放 神经系统和脾脏，并将这些结果转化为哺乳动物模型 到项目期结束时。