A MicroRNA-Based Gene-Targeting Tool for Virally Labeling Interneurons in the Rodent Cortex

Cell Rep. 2018 Jul 10;24(2):294-303. doi: 10.1016/j.celrep.2018.06.049.


More specific and broadly applicable viral gene-targeting tools for labeling neuron subtypes are needed to advance neuroscience research, especially in rodent transgenic disease models and genetically intractable species. Here, we develop a viral vector that restricts transgene expression to GABAergic interneurons in the rodent neocortex by exploiting endogenous microRNA regulation. Our interneuron-targeting, microRNA-guided neuron tag, "GABA mAGNET," achieves >95% interneuron selective labeling in the mouse cortex, including in a murine model of autism and also some preferential labeling of interneurons in the rat brain. We demonstrate an application of our GABA mAGNET by performing simultaneous, in vivo optogenetic control of two distinct neuron subtypes. This interneuron labeling tool highlights the potential of microRNA-based viral gene targeting to specific neuron subtypes.

Keywords: AAV; GABAergic; autism; gene targeting; gene therapy; genetic labeling; interneurons; lentivirus; mAGNET; microRNA; mouse; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Autistic Disorder / pathology
  • Cerebral Cortex / metabolism*
  • Dependovirus / metabolism
  • Disease Models, Animal
  • Gene Targeting*
  • Humans
  • Interneurons / metabolism*
  • Lentivirus / metabolism*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neurons / metabolism
  • Neurons / pathology
  • Optogenetics
  • Rats
  • Staining and Labeling*
  • Synapsins / genetics
  • gamma-Aminobutyric Acid / metabolism


  • MicroRNAs
  • Synapsins
  • gamma-Aminobutyric Acid