Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Rev Neurosci. 2020 Dec;21(12):669-681. doi: 10.1038/s41583-020-00382-z. Epub 2020 Oct 27.
Recombinant viruses are the workhorse of modern neuroscience. Whether one would like to understand a neuron's morphology, natural activity patterns, molecular composition, connectivity or behavioural and physiologic function, most studies begin with the injection of an engineered virus, often an adeno-associated virus or herpes simplex virus, among many other types. Recombinant viruses currently enable some combination of cell type-specific, circuit-selective, activity-dependent and spatiotemporally resolved transgene expression. Viruses are now used routinely to study the molecular and cellular functions of a gene within an identified cell type in the brain, and enable the application of optogenetics, chemogenetics, calcium imaging and related approaches. These advantageous properties of engineered viruses thus enable characterization of neuronal function at unprecedented resolution. However, each virus has specific advantages and disadvantages, which makes viral tool selection paramount for properly designing and executing experiments within the central nervous system. In the current Review, we discuss the key principles and uses of engineered viruses and highlight innovations that are needed moving forward.
重组病毒是现代神经科学的主要工具。无论是要了解神经元的形态、自然活动模式、分子组成、连接还是行为和生理功能,大多数研究都是从注射工程病毒开始的,通常是腺相关病毒或单纯疱疹病毒,还有许多其他类型的病毒。重组病毒目前能够实现细胞类型特异性、回路选择性、活动依赖性和时空分辨的转基因表达的某种组合。病毒现在被常规用于研究大脑中特定细胞类型内基因的分子和细胞功能,并能够应用光遗传学、化学生物学、钙成像和相关方法。因此,这些工程病毒的优势特性使神经元功能的表征达到了前所未有的分辨率。然而,每种病毒都有其特定的优缺点,这使得病毒工具的选择对于在中枢神经系统中正确设计和执行实验至关重要。在本期综述中,我们讨论了工程病毒的关键原则和用途,并强调了前进所需的创新。