CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory

Abstract
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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.

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Miou Zhou

Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Stuart Greenhill

Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5038-5258
Shan Huang

Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
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.
Yoshitake Sano

Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
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.
Ying Cai

Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Yoshiko Nagaoka

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States

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The authors declare that no competing interests exist.
Megha Sehgal

Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
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.
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.
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.
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.

"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.

Copyright

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.