Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA.
Science. 2024 Sep 27;385(6716):eadn6671. doi: 10.1126/science.adn6671.
To determine how neuronal circuits encode and drive behavior, it is often necessary to measure and manipulate different aspects of neurochemical signaling in awake animals. Optogenetics and calcium sensors have paved the way for these types of studies, allowing for the perturbation and readout of spiking activity within genetically defined cell types. However, these methods lack the ability to further disentangle the roles of individual neuromodulator and neuropeptides on circuits and behavior. We review recent advances in chemical biology tools that enable precise spatiotemporal monitoring and control over individual neuroeffectors and their receptors in vivo. We also highlight discoveries enabled by such tools, revealing how these molecules signal across different timescales to drive learning, orchestrate behavioral changes, and modulate circuit activity.
为了确定神经元回路如何对行为进行编码和驱动，通常有必要在清醒动物中测量和操纵神经化学信号传递的不同方面。光遗传学和钙传感器为这些类型的研究铺平了道路，使人们能够在遗传定义的细胞类型中对尖峰活动进行干扰和读取。然而，这些方法缺乏进一步区分单个神经调质和神经肽在回路和行为中的作用的能力。我们回顾了化学生物学工具的最新进展，这些工具能够在体内精确监测和控制单个神经效应器及其受体的时空分布。我们还强调了这些工具所带来的发现，揭示了这些分子如何在不同时间尺度上传递信号，以驱动学习、协调行为变化和调节回路活动。
