1. Neuroscience
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CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

  1. Miou Zhou
  2. Stuart Greenhill
  3. Shan Huang
  4. Tawnie K Silva
  5. Yoshitake Sano
  6. Shumin Wu
  7. Ying Cai
  8. Yoshiko Nagaoka
  9. Megha Sehgal
  10. Denise J Cai
  11. Yong-Seok Lee
  12. Kevin Fox  Is a corresponding author
  13. Alcino J Silva  Is a corresponding author
  1. University of California, Los Angeles, United States
  2. Cardiff University, United Kingdom
Research Article
  • Cited 40
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Cite this article as: eLife 2016;5:e20985 doi: 10.7554/eLife.20985

Abstract

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity. These results suggest that CCR5 is a powerful suppressor for plasticity and memory, and CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits. Consistent with this hypothesis, the HIV V3 peptide caused LTP, signaling and memory deficits that were prevented by Ccr5 knockout or knockdown. Overall, our results demonstrate that CCR5 plays an important role in neuroplasticity, learning and memory, and indicate that CCR5 has a role in the cognitive deficits caused by HIV.

Article and author information

Author details

  1. Miou Zhou

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Stuart Greenhill

    Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5038-5258
  3. Shan Huang

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tawnie K Silva

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yoshitake Sano

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shumin Wu

    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ying Cai

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Yoshiko Nagaoka

    Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Megha Sehgal

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Denise J Cai

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Yong-Seok Lee

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Kevin Fox

    Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom
    For correspondence
    foxkd@cardiff.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  13. Alcino J Silva

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    silvaa@mednet.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1587-4558

Funding

National Institute of Mental Health (P50-MH0779720)

  • Alcino J Silva

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

  • Alcino J Silva

Medical Research Council (G0901299)

  • Kevin Fox

National Institute of Mental Health (P50-MH0779720)

  • Kevin Fox

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed during the light phase of the cycle. All studies were approved by the UCLA Institutional Animal Care and Use Committee, also known as the Chancellor's Animal Research Committee (ARC, protocol# 1998-070), and by University of Cardiff and carried out in compliance with the United Kingdom's Animals (Scientific Procedures) Act 1986 where applicable.

Reviewing Editor

  1. Moses V Chao, New York University Langone Medical Center, United States

Publication history

  1. Received: August 26, 2016
  2. Accepted: December 19, 2016
  3. Accepted Manuscript published: December 20, 2016 (version 1)
  4. Version of Record published: January 5, 2017 (version 2)

Copyright

© 2016, Zhou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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