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

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  • Abbas, Atheir I.
    • Other Affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA
  • Moy, Sheryl S
    • Affiliation: School of Medicine, Department of Psychiatry, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Hartmann, John
    • Affiliation: School of Medicine
  • Pei, Ying
    • Affiliation: School of Medicine, Department of Pharmacology
  • Roth, Bryan
    • ORCID: https://orcid.org/0000-0002-0561-6536
    • Affiliation: School of Medicine, Department of Pharmacology, UNC Neuroscience Center, Neuroscience Curriculum, Eshelman School of Pharmacy, Center for Integrative Chemical Biology and Drug Discovery, Neuroscience Center, Division of Chemical Biology and Medicinal Chemistry, Department of Psychiatry, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
    • Other Affiliation: National Institute of Mental Health Psychoactive Drug Screening Program, Duke University, Durham, NC 27710, USA
  • Nicolelis, Miguel A.
    • Other Affiliation: Department of Neurobiology, Duke University, Durham, NC 27710, USA
  • Armbruster, Blaine N.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Alexander, Georgia M.
    • Other Affiliation: Department of Neurobiology, Duke University, Durham, NC 27710, USA
  • Allen, John A.
    • Affiliation: School of Medicine, Department of Pharmacology, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • Rogan, Sarah C.
    • Affiliation: School of Medicine, Department of Pharmacology
  • Nonneman, Randal J
    • Affiliation: School of Medicine, Neurodevelopment Disorders Research Center, Carolina Institute for Developmental Disabilities
  • McNamara, James O.
    • Other Affiliation: Department of Neurobiology, Duke University, Durham, NC 27710, USA
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.
Date of publication
Identifier
  • 2-s2.0-68349103200
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Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Neuron
Journal volume
  • 63
Journal issue
  • 1
Page start
  • 27
Page end
  • 39
Language
  • English
Version
  • Postprint
ISSN
  • 0896-6273
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