Optical Nanosensors Detect Neurotransmitter Release in the Peripheral Nervous System

摘要 最近的证据表明，免疫系统和免疫系统之间的沟通， 大脑对控制炎症至关重要。大脑接收信息是对受伤的反应 在外周引起炎症，这反过来又启动了一种反射机制，以抑制 免疫反应。由此产生的神经内分泌反射在以下方面起着重要的调节作用： 免疫系统.这些双向的脑-外周免疫通讯 反射性地，在一个封闭的反馈回路中，神经回路可以对 调节炎症。然而，这种脑免疫的具体机制 信号在很大程度上未知。因此，了解不同的分子和 控制这些复杂通路的神经生理机制是至关重要的， 我们需要开发新的方法来准确地检测和监测这些变化。我们将开发 用于检测周围神经系统中神经递质释放的纳米传感器 蝾螈（再生蝾螈）。我们的纳米传感器基于一个模块化平台， 可以容易地调谐到适当的动态范围、用于组织穿透的波长， 尺寸与体内环境相容。幼年美西螈是高度透明的， 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， 开发一种转基因模型，可以用光刺激靶向神经元兴奋，同时 通过从注射的神经递质发出的荧光同时测量神经递质水平， 纳米传感器结合起来，我们将图像体积释放乙酰胆碱在外周 神经系统和脾脏的美西螈，并将这些结果转化为哺乳动物模型 到项目结束时。

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.