TY - JOUR
T1 - Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors.
AU - Alexander, Georgia M.
AU - Rogan, Sarah C.
AU - Abbas, Atheir I.
AU - Armbruster, Blaine N.
AU - Pei, Ying
AU - Allen, John A.
AU - Nonneman, Randal J.
AU - Hartmann, John
AU - Moy, Sheryl S.
AU - Nicolelis, Miguel A.
AU - McNamara, James O.
AU - Roth, Bryan L.
N1 - Funding Information:
This work was supported by the following awards from the National Institutes of Health: NS060326 from the National Institute of Neurological Disease and Stroke (G.M.A.), GM07040-34 and GM008719 from the National Institute of General Medical Sciences (S.C.R.), GM007250 from the National Institute of General Medical Sciences (A.I.A.), GM074554 from the National Institute of General Medical Sciences (B.N.A.), HD040127 from the National Institute of Child Health and Human Development (J.A.A.), HD03110 from the National Institute of Child Health and Human Development (R.J.N., S.S.M.), NS049534 from the National Institutes of Neurological Disorders and Stroke (M.A.N.), NS056217 from the National Institute of Neurological Disease and Stroke (J.O.M.), and MH082441-02 from the National Institute of Mental Health (B.L.R.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. This work is also supported by a NARSAD Distinguished Investigator Award (B.L.R.).
PY - 2009/7/16
Y1 - 2009/7/16
N2 - 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.
AB - 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.
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U2 - 10.1016/j.neuron.2009.06.014
DO - 10.1016/j.neuron.2009.06.014
M3 - Article
C2 - 19607790
AN - SCOPUS:68349103200
SN - 0896-6273
VL - 63
SP - 27
EP - 39
JO - Neuron
JF - Neuron
IS - 1
ER -