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

Miou Zhou, Stuart Greenhill, Shan Huang, Tawnie K. Silva, Yoshitake Sano, Shumin Wu, Ying Cai, Yoshiko Nagaoka, Megha Sehgal, Denise J. Cai, Yong-Seok Lee, Kevin Fox*, Alcino J. Silva

*Corresponding author for this work

Research output: Contribution to journalArticle

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.
Original languageEnglish
Article numbere20985
Number of pages30
JournaleLife
Volume5
DOIs
Publication statusPublished - 20 Dec 2016

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Keywords

  • neuroscience
  • plasticity
  • HIV
  • dementia

Cite this

Zhou, M., Greenhill, S., Huang, S., Silva, T. K., Sano, Y., Wu, S., ... Silva, A. J. (2016). CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory. eLife, 5, [e20985]. https://doi.org/10.7554/eLife.20985