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

• Published in: Neuroscience Vol. 161; no. 2; pp. 441 - 450
• Main Authors: Nathanson, J.L, Yanagawa, Y, Obata, K, Callaway, E.M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 30.06.2009; Elsevier
• Subjects: AAV; Adeno-associated virus; Animals; Biological and medical sciences; cortex; Dependovirus - genetics; Fundamental and applied biological sciences. Psychology; Gene Knock-In Techniques; Genetic Vectors; Glutamate Decarboxylase - genetics; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Humans; Lentivirus; Lentivirus - genetics; Mice; Mice, Mutant Strains; mouse; Neurology; neurons; Neurons - metabolism; Promoter Regions, Genetic; Somatosensory Cortex - cytology; Somatosensory Cortex - metabolism; Synapsins - genetics; Transduction, Genetic; tropism; Vertebrates: nervous system and sense organs; Vesicular stomatitis virus; recombinant AAV with serotype 2 backbone packaged with serotype 1 capsid; VSV-G-LV; hybrid CMV/chicken β-actin promoter; vesicular stomatitis virus; LV; adeno-associated virus; neurons; GFP; mouse; red fluorescent protein; neuronal nuclei antibody; lentivirus pseudotyped with vesicular stomatitis virus glycoprotein; RFP; lentivirus; cortex; WPRE; tropism; CAG; glutamate decarboxylase 67; GAD67; green fluorescent protein; woodchuck hepatitis virus posttranscriptional regulatory element; mouse α-calcium/calmodulin-dependent protein kinase II promoter; hSyn; human synapsin I promoter; NeuN; AAV; mCAMK; VSV; rAAV2/1; Vertebrata; Mammalia; Neuron; Mouse; Animal; Rodentia
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.03.032

Abstract 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.