CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory
- University of California, Los Angeles, United States
- Cardiff University, United Kingdom
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
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.
Reviewing Editor
- Moses V Chao, New York University Langone Medical Center, United States
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.
Version history
- Received: August 26, 2016
- Accepted: December 19, 2016
- Accepted Manuscript published: December 20, 2016 (version 1)
- 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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CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory
eLife 5:e20985.
https://doi.org/10.7554/eLife.20985
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