Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors

Neuroscience. 2009 Jun 30;161(2):441-50. doi: 10.1016/j.neuroscience.2009.03.032. Epub 2009 Mar 24.


Despite increasingly widespread use of recombinant adeno-associated virus (AAV) and lentiviral (LV) vectors for transduction of neurons in a wide range of brain structures and species, the diversity of cell types within a given brain structure is rarely considered. For example, the ability of a vector to transduce neurons within a brain structure is often assumed to indicate that all neuron types within the structure are transduced. We have characterized the transduction of mouse somatosensory cortical neuron types by recombinant AAV pseudotyped with serotype 1 capsid (rAAV2/1) and by recombinant lentivirus pseudotyped with the vesicular stomatitis virus (VSV) glycoprotein. Both vectors used human synapsin (hSyn) promoter driving DsRed-Express. We demonstrate that high titer rAAV2/1-hSyn efficiently transduces both cortical excitatory and inhibitory neuronal populations, but use of lower titers exposes a strong preference for transduction of cortical inhibitory neurons and layer 5 pyramidal neurons. In contrast, we find that VSV-G-LV-hSyn principally labels excitatory cortical neurons at the highest viral titer generated. These findings demonstrate that endogenous tropism of rAAV2/1 and VSV-G-LV can be used to obtain preferential gene expression in mouse somatosensory cortical inhibitory and excitatory neuron populations, respectively.

Publication types

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

MeSH terms

  • Animals
  • Dependovirus / genetics*
  • Gene Knock-In Techniques
  • Genetic Vectors
  • Glutamate Decarboxylase / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Lentivirus / genetics*
  • Mice
  • Mice, Mutant Strains
  • Neurons / metabolism*
  • Promoter Regions, Genetic
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / metabolism*
  • Synapsins / genetics
  • Transduction, Genetic


  • Synapsins
  • Green Fluorescent Proteins
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1