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基于影像的化学遗传学在非人类灵长类动物中解析神经回路。

Imaging-based chemogenetics for dissecting neural circuits in nonhuman primates.

机构信息

Advanced Neuroimaging Center, National Institutes for Quantum Science and Technology, Chiba, Japan.

出版信息

Proc Jpn Acad Ser B Phys Biol Sci. 2024;100(8):476-489. doi: 10.2183/pjab.100.030.

Abstract

Nonhuman primates, particularly macaque and marmoset monkeys, serve as invaluable models for studying complex brain functions and behavior. However, the lack of suitable genetic neuromodulation tools has constrained research at the network level. This review examines the application of a chemogenetic technology, specifically, designer receptors exclusively activated by designer drugs (DREADDs), to nonhuman primates. DREADDs offer a means of reversibly controlling neuronal activity within a specific cell type or neural pathway, effectively targeting multiple brain regions simultaneously. The combination of DREADDs with imaging techniques, such as positron emission tomography and magnetic resonance imaging, has significantly enhanced nonhuman primate research, facilitating the precise visualization and manipulation of specific brain circuits and enabling the detailed monitoring of changes in network activity, which can then be correlated with altered behavior. This review outlines these technological advances and considers their potential for enhancing our understanding of primate brain circuit function and developing novel therapeutic approaches for treating brain diseases.

摘要

非人类灵长类动物,特别是猕猴和狨猴,是研究复杂大脑功能和行为的宝贵模型。然而,缺乏合适的遗传神经调节工具限制了网络水平的研究。本综述探讨了一种化学遗传学技术的应用,即专门被设计药物激活的设计受体(DREADDs)在非人类灵长类动物中的应用。DREADDs 提供了一种在特定细胞类型或神经通路内可逆控制神经元活动的方法,可有效地同时靶向多个脑区。DREADDs 与成像技术(如正电子发射断层扫描和磁共振成像)相结合,极大地促进了非人类灵长类动物的研究,能够精确地可视化和操作特定的大脑回路,并详细监测网络活动的变化,然后可以将其与行为改变相关联。本综述概述了这些技术进步,并考虑了它们在增强我们对灵长类大脑回路功能的理解以及开发治疗脑部疾病的新治疗方法方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd2/11535006/7aa38c5fc2c7/pjab-100-476-g001.jpg

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