The Use of DREADDs to Deconstruct Behavior.
The Use of DREADDs to Deconstruct Behavior.
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DOI：
10.3389/fgene.2016.00070
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发表时间：
2016
影响因子：
3.7
通讯作者：
Martin LJ
中科院分区：
文献类型：
--
作者：
Whissell PD;Tohyama S;Martin LJ
理解大脑功能的一个中心目标是将特定的细胞群与行为输出联系起来。近年来，随着化学遗传学等新实验方法的发展，选择性靶向特定神经回路成为可能。这项技术允许通过工程G蛋白偶联受体（gpcr）控制分子定义的细胞亚群，gpcr具有激活或沉默神经元放电的能力。通过化学遗传学，神经回路正以前所未有的速度与行为输出联系起来。此外，结合化学遗传学和成像技术来监测自由运动动物的神经活动，现在有可能解构复杂的全脑网络，这是行为状态的基础。在这篇综述中，我们重点介绍了一种特殊的化学遗传学应用，称为DREADDs（设计物药物特异性激活的设计物受体）。reads在体内被广泛用于调控GPCR活性，在基础科学，特别是行为神经科学领域得到了广泛的应用。在这里，我们关注的是DREADD技术在剖析包括记忆、认知、奖励、进食、焦虑和疼痛在内的各种行为的神经回路中的影响和效用。通过使用DREADDs来监测特定神经元类型的电生理、生化和行为输出，研究人员可以更好地了解大脑活动和行为之间的联系。此外，DREADDs在研究疾病的发病机制方面是有用的，并可能最终具有治疗潜力。
A central goal in understanding brain function is to link specific cell populations to behavioral outputs. In recent years, the selective targeting of specific neural circuits has been made possible with the development of new experimental approaches, including chemogenetics. This technique allows for the control of molecularly defined subsets of cells through engineered G protein-coupled receptors (GPCRs), which have the ability to activate or silence neuronal firing. Through chemogenetics, neural circuits are being linked to behavioral outputs at an unprecedented rate. Further, the coupling of chemogenetics with imaging techniques to monitor neural activity in freely moving animals now makes it possible to deconstruct the complex whole-brain networks that are fundamental to behavioral states. In this review, we highlight a specific chemogenetic application known as DREADDs (designer receptors exclusively activated by designer drugs). DREADDs are used ubiquitously to modulate GPCR activity in vivo and have been widely applied in the basic sciences, particularly in the field of behavioral neuroscience. Here, we focus on the impact and utility of DREADD technology in dissecting the neural circuitry of various behaviors including memory, cognition, reward, feeding, anxiety and pain. By using DREADDs to monitor the electrophysiological, biochemical, and behavioral outputs of specific neuronal types, researchers can better understand the links between brain activity and behavior. Additionally, DREADDs are useful in studying the pathogenesis of disease and may ultimately have therapeutic potential.