Fralin Biomedical Research Institute, Translational Biology, Medicine and Health, Roanoke, VA, USA.
Department of Biology, Pennsylvania State University, College Park, PA, USA; Center for the Molecular Investigation of Neurological Disorders (CMIND), Pennsylvania State University, College Park, PA, USA.
Neurosci Biobehav Rev. 2020 Jan;108:732-748. doi: 10.1016/j.neubiorev.2019.12.013. Epub 2019 Dec 13.
The past decade has produced an explosion in the number and variety of genetic tools available to neuroscientists, resulting in an unprecedented ability to precisely manipulate the genome and epigenome in behaving animals. However, no single resource exists that describes all of the tools available to neuroscientists. Here, we review the genetic, transgenic, and viral techniques that are currently available to probe the complex relationship between genes and cognition. Topics covered include types of traditional transgenic mouse models (knockout, knock-in, reporter lines), inducible systems (Cre-loxP, Tet-On, Tet-Off) and cell- and circuit-specific systems (TetTag, TRAP, DIO-DREADD). Additionally, we provide details on virus-mediated and siRNA/shRNA approaches, as well as a comprehensive discussion of the myriad manipulations that can be made using the CRISPR-Cas9 system, including single base pair editing and spatially- and temporally-regulated gene-specific transcriptional control. Collectively, this review will serve as a guide to assist neuroscientists in identifying and choosing the appropriate genetic tools available to study the complex relationship between the brain and behavior.
过去十年中，神经科学家可用的遗传工具的数量和种类呈爆炸式增长，使得他们能够以前所未有的精确性在行为动物中操纵基因组和表观基因组。然而，目前还没有一个资源能够描述神经科学家可用的所有工具。在这里，我们回顾了目前可用于探究基因与认知之间复杂关系的遗传、转基因和病毒技术。所涵盖的主题包括传统转基因小鼠模型（敲除、敲入、报告基因系）、诱导系统（Cre-loxP、Tet-On、Tet-Off）和细胞及回路特异性系统（TetTag、TRAP、DIO-DREADD）的类型。此外，我们还提供了病毒介导和 siRNA/shRNA 方法的详细信息，以及使用 CRISPR-Cas9 系统进行的无数种操作的综合讨论，包括单碱基编辑和空间和时间调节的基因特异性转录控制。总的来说，这篇综述将作为一个指南，帮助神经科学家识别和选择适当的遗传工具，以研究大脑和行为之间的复杂关系。
