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

Georgia M. Alexander, Sarah C. Rogan, Atheir I. Abbas, Blaine N. Armbruster, Ying Pei, John A. Allen, Randal J. Nonneman, John Hartmann, Sheryl S. Moy, Miguel A. Nicolelis, James O. McNamara, Bryan L. Roth

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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.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalNeuron
Volume63
Issue number1
StatePublished - Jul 16 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alexander, G. M., Rogan, S. C., Abbas, A. I., Armbruster, B. N., Pei, Y., Allen, J. A., Nonneman, R. J., Hartmann, J., Moy, S. S., Nicolelis, M. A., McNamara, J. O., & Roth, B. L. (2009). Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron, 63(1), 27-39.