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.
journal_name
Neuronjournal_title
Neuronauthors
Alexander GM,Rogan SC,Abbas AI,Armbruster BN,Pei Y,Allen JA,Nonneman RJ,Hartmann J,Moy SS,Nicolelis MA,McNamara JO,Roth BLdoi
10.1016/j.neuron.2009.06.014subject
Has Abstractpub_date
2009-07-16 00:00:00pages
27-39issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(09)00467-Xjournal_volume
63pub_type
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