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Cell Rep. 2019 Mar 5;26(10):2818-2832.e8. doi: 10.1016/j.celrep.2019.02.011.

Functional Access to Neuron Subclasses in Rodent and Primate Forebrain.

Author information

1
Center for Learning and Memory, University of Texas, Austin, TX 78712, USA; Department of Neuroscience, University of Texas, Austin, TX 78712, USA.
2
Center for Computational Biology and Bioinformatics, University of Texas, Austin, TX 78712, USA.
3
Center for Learning and Memory, University of Texas, Austin, TX 78712, USA; Center for Perceptual Systems, University of Texas, Austin, TX 78712, USA; Department of Neuroscience, University of Texas, Austin, TX 78712, USA.
4
Kavli Institute for Brain Science, Columbia University, New York, NY 10027, USA; Department of Neuroscience, Columbia University, New York, NY 10027, USA.
5
Center for Perceptual Systems, University of Texas, Austin, TX 78712, USA; Department of Neuroscience, University of Texas, Austin, TX 78712, USA; Department of Psychology, University of Texas, Austin, TX 78712, USA.
6
Center for Learning and Memory, University of Texas, Austin, TX 78712, USA; Department of Neuroscience, University of Texas, Austin, TX 78712, USA. Electronic address: zemelmanb@mail.clm.utexas.edu.

Abstract

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.

KEYWORDS:

adeno-associated virus; cell type-specific promoter; functional in vivo imaging; inhibitory neurons; macaque; marmoset; neuropeptide-Y; parvalbumin; rodent; somatostatin

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