Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.
Genetically encoded sensors towards imaging cAMP and PKA activity in vivo.
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DOI：
10.1016/j.jneumeth.2021.109298
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发表时间：
2021-10-01
影响因子：
3
通讯作者：
Zhong H
中科院分区：
文献类型：
--
作者：
Massengill CI;Day-Cooney J;Mao T;Zhong H
环磷酸腺苷（cAMP）是一种通用的第二信使，在从转录到神经元可塑性以及从发育到学习和记忆的各种生物功能中起着至关重要的作用。在神经系统中，cAMP整合了许多神经调质在广泛的时间范围内（从几秒到几小时）的输入，以调节不同动物行为状态期间脑回路中的神经元兴奋性和可塑性。cAMP信号传导事件是细胞特异性的和亚细胞区室化的。相同的刺激可能导致不同的，有时相反的，在不同的细胞或亚细胞区室的cAMP动力学。此外，蛋白激酶A（PKA）的活性，一个主要的cAMP效应，也时空调节。由于这些原因，许多实验室已经在可视化cAMP和PKA的细胞内动力学方面取得了很大进展。迄今为止，已经发表了80多种基因编码传感器，包括原始和改进的变体。它开始成为可能，以可视化cAMP和PKA信号在体内的事件，这是需要研究行为相关的cAMP/PKA信号机制。尽管取得了重大进展，但需要进一步发展，以提高这些传感器的信噪比和实际效用。本文综述了基因编码的cAMP和PKA传感器的最新进展和挑战，重点是在行为过程中在脑中的体内成像。
Cyclic adenosine monophosphate (cAMP) is a universal second messenger that plays a crucial role in diverse biological functions, ranging from transcription to neuronal plasticity, and from development to learning and memory. In the nervous system, cAMP integrates inputs from many neuromodulators across a wide range of timescales — from seconds to hours — to modulate neuronal excitability and plasticity in brain circuits during different animal behavioral states. cAMP signaling events are both cell-specific and subcellularly compartmentalized. The same stimulus may result in different, sometimes opposite, cAMP dynamics in different cells or subcellular compartments. Additionally, the activity of protein kinase A (PKA), a major cAMP effector, is also spatiotemporally regulated. For these reasons, many laboratories have made great strides toward visualizing the intracellular dynamics of cAMP and PKA. To date, more than 80 genetically encoded sensors, including original and improved variants, have been published. It is starting to become possible to visualize cAMP and PKA signaling events in vivo, which is required to study behaviorally relevant cAMP/PKA signaling mechanisms. Despite significant progress, further developments are needed to enhance the signal-to-noise ratio and practical utility of these sensors. This review summarizes the recent advances and challenges in genetically encoded cAMP and PKA sensors with an emphasis on in vivo imaging in the brain during behavior.
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