El-Shamayleh Yasmine, Ni Amy M, Horwitz Gregory D
Department of Physiology and Biophysics and Washington National Primate Research Center, University of Washington, Seattle, Washington; and.
Department of Neuroscience and Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania.
J Neurophysiol. 2016 Jul 1;116(1):122-34. doi: 10.1152/jn.00087.2016. Epub 2016 Apr 6.
Understanding how the brain works requires understanding how different types of neurons contribute to circuit function and organism behavior. Progress on this front has been accelerated by optogenetics and chemogenetics, which provide an unprecedented level of control over distinct neuronal types in small animals. In primates, however, targeting specific types of neurons with these tools remains challenging. In this review, we discuss existing and emerging strategies for directing genetic manipulations to targeted neurons in the adult primate central nervous system. We review the literature on viral vectors for gene delivery to neurons, focusing on adeno-associated viral vectors and lentiviral vectors, their tropism for different cell types, and prospects for new variants with improved efficacy and selectivity. We discuss two projection targeting approaches for probing neural circuits: anterograde projection targeting and retrograde transport of viral vectors. We conclude with an analysis of cell type-specific promoters and other nucleotide sequences that can be used in viral vectors to target neuronal types at the transcriptional level.
了解大脑如何工作需要了解不同类型的神经元如何对神经回路功能和机体行为产生影响。光遗传学和化学遗传学加速了这方面的进展，它们为控制小型动物中不同类型的神经元提供了前所未有的水平。然而，在灵长类动物中，使用这些工具靶向特定类型的神经元仍然具有挑战性。在这篇综述中，我们讨论了将基因操作导向成年灵长类动物中枢神经系统中靶向神经元的现有策略和新兴策略。我们回顾了关于用于向神经元递送基因的病毒载体的文献，重点是腺相关病毒载体和慢病毒载体、它们对不同细胞类型的嗜性，以及具有更高疗效和选择性的新变体的前景。我们讨论了两种用于探测神经回路的投射靶向方法：顺行投射靶向和病毒载体的逆行运输。我们最后分析了可用于病毒载体以在转录水平靶向神经元类型的细胞类型特异性启动子和其他核苷酸序列。
