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Elife. 2016 Dec 20;5. pii: e20985. doi: 10.7554/eLife.20985.

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

Author information

1
Departments of Neurobiology, Psychology, Psychiatry, Integrative Center for Learning and Memory and Brain Research Institute, University of California, Los Angeles, Los Angeles, United States.
2
Cardiff School of Biosciences, Cardiff University, Cardiff, United Kingdom.
3
School of Life and Health Sciences, Aston University, Birmingham, United Kingdom.
4
Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.
5
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, United States.
6
Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.

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.

KEYWORDS:

CCR5; HIV-associated cognitive deficits; barrel cortex; gp120; hippocampus; learning and memory; mouse; neuroscience

PMID:
27996938
PMCID:
PMC5213777
DOI:
10.7554/eLife.20985
[Indexed for MEDLINE]
Free PMC Article

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