美国加州大学洛杉矶分校Alcino J. Silva和Miou Zhou研究组合作揭示，C-C 趋化因子受体 5 (CCR5)可关闭记忆链接的时间窗口。相关论文发表在2022年5月25日出版的《自然》杂志上。
他们展示了CCR5（一种免疫受体，众所周知是 HIV 感染的共同受体）的表达延迟（12-24 小时）增加在环境记忆形成后决定时间窗口的持续时间，以便将该记忆与后续记忆关联或链接。小鼠背侧 CA1 神经元中 CCR5 的这种延迟表达导致神经元兴奋性降低，进而负调节神经元记忆分配，从而减少背侧 CA1 记忆集合之间的重叠。降低这种重叠会影响一个记忆触发另一个记忆的召回能力，因此关闭记忆链接的时间窗口。
他们的研究结果还表明，与年龄相关的 CCR5 及其配体 CCL5 的神经元表达增加会导致老年小鼠的记忆连接受损，这可以通过 Ccr5 敲除和美国食品和药物管理局（FDA）批准的药物逆转。抑制这种受体具有临床意义。总而言之，这里报道的研究结果提供了对塑造记忆链接时间窗口的分子和细胞机制的见解。
据介绍，现实世界的记忆是在特定的环境下形成的，通常不是孤立地获得或回忆的。时间是记忆组织中的一个关键变量，因为时间接近的事件更有可能有意义地关联，而间隔较长的事件则不是。大脑如何区分时间上不同的事件尚不清楚。
附：英文原文
Title: CCR5 closes the temporal window for memory linking
Author: Shen, Yang, Zhou, Miou, Cai, Denise, Filho, Daniel Almeida, Fernandes, Giselle, Cai, Ying, de Sousa, Andr F., Tian, Min, Kim, Nury, Lee, Jinsu, Necula, Deanna, Zhou, Chengbin, Li, Shuoyi, Salinas, Shelbi, Liu, Andy, Kang, Xiaoman, Kamata, Masakazu, Lavi, Ayal, Huang, Shan, Silva, Tawnie, Do Heo, Won, Silva, Alcino J.
Issue&Volume: 2022-05-25
Abstract: Real-world memories are formed in a particular context and are often not acquired or recalled in isolation1,2,3,4,5. 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 not1,2,3,4. How the brain segregates events that are temporally distinct is unclear. Here we show that a delayed (12–24h) 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.
DOI: 10.1038/s41586-022-04783-1
Source: https://www.nature.com/articles/s41586-022-04783-1
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
