The brain is composed of complex neuronal networks that interact on spatial and temporal scales that span several orders of magnitude. Uncovering how this circuitry gives rise to multifaceted phenomena such as perception, memory, and behavior remains one of the grand challenges in science today. A wide range of investigative methods have been developed to delve deeper into the inner workings of the brain, spanning the realms of molecular biology, genetics, chemistry, optics, and engineering, thereby forming a nexus of discovery that has accelerated our understanding of the brain. Whereas neuronal electrical excitability is a hallmark property of neurons, chemical signaling between neurons—mediated by hundreds of neurotransmitters, neuromodulators, hormones, and other signaling molecules—is equally important, but far more elusive in its regulation of brain function for motor control, learning, and behavior. To date, the brain's neurochemical state has been interrogated using classical tools borrowed from analytical chemistry, such as liquid chromatography and amperometry, and more recently, newly developed fluorescent sensors. Here, the authors review advances in the development of functional fluorescent probes that are beginning to expand their understanding of the neurochemical basis of brain function alongside device-based analytical tools that have already made extensive contributions to the field. The emphasis herein is on the paradigms of probe and device development, which follow certain design principles unique to the interrogation of brain chemistry.

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评论文章：探测大脑神经化学的工具和趋势

大脑由复杂的神经元网络组成，这些神经元网络在跨越几个数量级的空间和时间尺度上相互作用。揭示这种电路如何产生感知、记忆和行为等多方面的现象仍然是当今科学面临的巨大挑战之一。人们已经开发出多种研究方法来深入研究大脑的内部运作，涵盖分子生物学、遗传学、化学、光学和工程学领域，从而形成了一系列的发现，加速了我们对大脑的理解。虽然神经元电兴奋性是神经元的一个标志特性，但神经元之间的化学信号传导（由数百种神经递质、神经调节剂、激素和其他信号分子介导）同样重要，但在调节大脑功能（例如运动控制、学习）方面更加难以捉摸。和行为。迄今为止，人们已经使用从分析化学借用的经典工具（例如液相色谱法和电流分析法）以及最近开发的荧光传感器来询问大脑的神经化学状态。在这里，作者回顾了功能性荧光探针的开发进展，这些探针开始扩大他们对大脑功能的神经化学基础的理解，同时基于设备的分析工具已经对该领域做出了广泛的贡献。本文的重点是探针和设备开发的范例，这些范例遵循大脑化学询问所特有的某些设计原则。