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CCR5 closes the temporal window for memory linking

Author

Listed:
  • Yang Shen

    (University of California Los Angeles)

  • Miou Zhou

    (University of California Los Angeles
    Western University of Health Sciences)

  • Denise Cai

    (University of California Los Angeles
    Icahn School of Medicine)

  • Daniel Almeida Filho

    (University of California Los Angeles)

  • Giselle Fernandes

    (University of California Los Angeles)

  • Ying Cai

    (University of California Los Angeles)

  • André F. Sousa

    (University of California Los Angeles)

  • Min Tian

    (University of California Los Angeles)

  • Nury Kim

    (Institute for Basic Science
    Korea Advanced Institute of Science and Technology)

  • Jinsu Lee

    (Korea Advanced Institute of Science and Technology)

  • Deanna Necula

    (University of California Los Angeles)

  • Chengbin Zhou

    (University of California Los Angeles)

  • Shuoyi Li

    (University of California Los Angeles)

  • Shelbi Salinas

    (Western University of Health Sciences)

  • Andy Liu

    (University of California Los Angeles)

  • Xiaoman Kang

    (University of California Los Angeles)

  • Masakazu Kamata

    (University of California Los Angeles)

  • Ayal Lavi

    (University of California Los Angeles)

  • Shan Huang

    (University of California Los Angeles)

  • Tawnie Silva

    (University of California Los Angeles)

  • Won Do Heo

    (Korea Advanced Institute of Science and Technology)

  • Alcino J. Silva

    (University of California Los Angeles)

Abstract

Real-world memories are formed in a particular context and are often not acquired or recalled in isolation1–5. Time is a key variable in the organization of memories, as events that are experienced close in time are more likely to be meaningfully associated, whereas those that are experienced with a longer interval are not1–4. How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12–24 h) increase in the expression of C-C chemokine receptor type 5 (CCR5)—an immune receptor that is well known as a co-receptor for HIV infection6,7—after the formation of a contextual memory determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed expression of CCR5 in mouse dorsal CA1 neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dorsal CA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, and therefore closes the temporal window for memory linking. Our findings also show that an age-related increase in the neuronal expression of CCR5 and its ligand CCL5 leads to impairments in memory linking in aged mice, which could be reversed with a Ccr5 knockout and a drug approved by the US Food and Drug Administration (FDA) that inhibits this receptor, a result with clinical implications. Altogether, the findings reported here provide insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.

Suggested Citation

  • Yang Shen & Miou Zhou & Denise Cai & Daniel Almeida Filho & Giselle Fernandes & Ying Cai & André F. Sousa & Min Tian & Nury Kim & Jinsu Lee & Deanna Necula & Chengbin Zhou & Shuoyi Li & Shelbi Salinas, 2022. "CCR5 closes the temporal window for memory linking," Nature, Nature, vol. 606(7912), pages 146-152, June.
  • Handle: RePEc:nat:nature:v:606:y:2022:i:7912:d:10.1038_s41586-022-04783-1
    DOI: 10.1038/s41586-022-04783-1
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    Cited by:

    1. Paul J. Lamothe-Molina & Andreas Franzelin & Lennart Beck & Dong Li & Lea Auksutat & Tim Fieblinger & Laura Laprell & Joachim Alhbeck & Christine E. Gee & Matthias Kneussel & Andreas K. Engel & Claus , 2022. "ΔFosB accumulation in hippocampal granule cells drives cFos pattern separation during spatial learning," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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