Center for Learning and Memory, University of Texas, Austin, TX 78712, USA; Department of Neuroscience, University of Texas, Austin, TX 78712, USA.
Center for Computational Biology and Bioinformatics, University of Texas, Austin, TX 78712, USA.
Cell Rep. 2019 Mar 5;26(10):2818-2832.e8. doi: 10.1016/j.celrep.2019.02.011.
Viral vectors enable foreign proteins to be expressed in brains of non-genetic species, including non-human primates. However, viruses targeting specific neuron classes have proved elusive. Here we describe viral promoters and strategies for accessing GABAergic interneurons and their molecularly defined subsets in the rodent and primate. Using a set intersection approach, which relies on two co-active promoters, we can restrict heterologous protein expression to cortical and hippocampal somatostatin-positive and parvalbumin-positive interneurons. With an orthogonal set difference method, we can enrich for subclasses of neuropeptide-Y-positive GABAergic interneurons by effectively subtracting the expression pattern of one promoter from that of another. These methods harness the complexity of gene expression patterns in the brain and significantly expand the number of genetically tractable neuron classes across mammals.
病毒载体使外源蛋白能够在非遗传物种的大脑中表达，包括非人类灵长类动物。然而，针对特定神经元类别的病毒一直难以捉摸。在这里，我们描述了用于靶向啮齿动物和灵长类动物中的 GABA 能中间神经元及其分子定义亚群的病毒启动子和策略。使用依赖于两个共同激活启动子的集合交集方法，我们可以将异源蛋白表达限制在皮质和海马体中的生长抑素阳性和钙结合蛋白阳性中间神经元上。通过正交集合差方法，我们可以通过从另一个启动子中有效地减去一个启动子的表达模式来富集神经肽 Y 阳性 GABA 能中间神经元的亚类。这些方法利用了大脑中基因表达模式的复杂性，并显著增加了跨哺乳动物的可遗传神经元类别的数量。
