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Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors

Authors :
Rogan, Sarah C.
Nonneman, Randal J
Moy, Sheryl S
Hartmann, John
Allen, John A.
Pei, Ying
Roth, Bryan
Armbruster, Blaine N.
Publication Year :
2009
Publisher :
The University of North Carolina at Chapel Hill University Libraries, 2009.

Abstract

Examining the behavioral consequences of selective CNS neuronal activation is a powerful tool for elucidating mammalian brain function in health and disease. Newly developed genetic, pharmacological, and optical tools allow activation of neurons with exquisite spatiotemporal resolution; however, the inaccessibility to light of widely distributed neuronal populations and the invasiveness required for activation by light or infused ligands limit the utility of these methods. To overcome these barriers, we created transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO). Here, we expressed hM3Dq in forebrain principal neurons. Local field potential and single-neuron recordings revealed that peripheral administration of CNO activated hippocampal neurons selectively in hM3Dq-expressing mice. Behavioral correlates of neuronal activation included increased locomotion, stereotypy, and limbic seizures. These results demonstrate a powerful chemical-genetic tool for remotely controlling the activity of discrete populations of neurons in vivo.

Subjects

Subjects :
nervous system

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi...........c01ec863bda5eadd535a11adf4c6eb24
Full Text :
https://doi.org/10.17615/h5rj-v360