Cell Reports (Mar 2019)

Functional Access to Neuron Subclasses in Rodent and Primate Forebrain

  • Preeti Mehta,
  • Lauren Kreeger,
  • Dennis C. Wylie,
  • Jagruti J. Pattadkal,
  • Tara Lusignan,
  • Matthew J. Davis,
  • Gergely F. Turi,
  • Wen-Ke Li,
  • Matthew P. Whitmire,
  • Yuzhi Chen,
  • Bridget L. Kajs,
  • Eyal Seidemann,
  • Nicholas J. Priebe,
  • Attila Losonczy,
  • Boris V. Zemelman

Journal volume & issue
Vol. 26, no. 10
pp. 2818 – 2832.e8

Abstract

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Summary: 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. : Mehta et al. describe methods for accessing inhibitory neuron subclasses in the mammalian forebrain. Keywords: inhibitory neurons, somatostatin, parvalbumin, neuropeptide-Y, cell type-specific promoter, adeno-associated virus, rodent, marmoset, macaque, functional in vivo imaging