High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression

Kuhlman, S. J., Huang, Z. J. (2008) High-resolution labeling and functional manipulation of specific neuron types in mouse brain by Cre-activated viral gene expression. PLoS ONE, 3 (4). e2005. ISSN 1932-6203 (Electronic)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/18414675
DOI: 10.1371/journal.pone.0002005

Abstract

We describe a method that combines Cre-recombinase knockin mice and viral-mediated gene transfer to genetically label and functionally manipulate specific neuron types in the mouse brain. We engineered adeno-associated viruses (AAVs) that express GFP, dsRedExpress, or channelrhodopsin (ChR2) upon Cre/loxP recombination-mediated removal of a transcription-translation STOP cassette. Fluorescent labeling was sufficient to visualize neuronal structures with synaptic resolution in vivo, and ChR2 expression allowed light activation of neuronal spiking. The structural dynamics of a specific class of neocortical neuron, the parvalbumin-containing (Pv) fast-spiking GABAergic interneuron, was monitored over the course of a week. We found that although the majority of Pv axonal boutons were stable in young adults, bouton additions and subtractions on axonal shafts were readily observed at a rate of 10.10% and 9.47%, respectively, over 7 days. Our results indicate that Pv inhibitory circuits maintain the potential for structural re-wiring in post-adolescent cortex. With the generation of an increasing number of Cre knockin mice and because viral transfection can be delivered to defined brain regions at defined developmental stages, this strategy represents a general method to systematically visualize the structure and manipulate the function of different cell types in the mouse brain.

Item Type: Paper
Additional Information:
Subjects: bioinformatics > genomics and proteomics > small molecules > GABAergic
Investigative techniques and equipment
organs, tissues, organelles, cell types and functions > organs types and functions > brain
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > green fluorescent protein
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

Investigative techniques and equipment > transfection
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: CSHL Librarian
Date Deposited: 10 Apr 2012 15:51
Last Modified: 10 Jan 2017 15:47
PMCID: PMC2289876
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25808

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