期刊
NEURON
卷 63, 期 1, 页码 27-39出版社
CELL PRESS
DOI: 10.1016/j.neuron.2009.06.014
关键词
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资金
- National Institute of Neurological Disease and Stroke [NS060326, NS049534, NS056217]
- National Institute of General Medical Sciences [GM07040-34, GM008719, GM007250, GM074554]
- National Institute of Child Health and Human Development [H0040127, HD03110]
- National Institute of Mental Health [MHO82441-02]
- NARSAD Distinguished InvestigatorAward
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 h1M3Dq-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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