美国康奈尔大学Azahara Oliva和Antonio Fernandez-Ruiz共同合作，近期取得重要工作进展。他们研究提出，睡眠微观结构组织记忆重放。相关研究成果2025年1月1日在线发表于《自然》杂志上。

据介绍，最近获得的记忆在睡眠期间在海马体中被重新激活，这是巩固记忆的第一步。这一过程伴随着海马体对先前记忆的重新激活，这就提出了如何防止旧记忆和近期获得的初期不稳定记忆痕迹之间的干扰问题。理论研究表明，通过随机交织多个记忆的重新激活，可以在最小化干扰的同时巩固多个记忆。另一种说法是，睡眠的时间微观结构可以在特定的亚状态下促进不同类型记忆的重新激活。

为了检验这两个假设，研究人员开发了一种方法，通过在自然睡眠的小鼠中进行瞳孔测量，同时记录大型海马体并监测睡眠动态。振荡性瞳孔波动揭示了一种以前未知的非快速眼动睡眠相关记忆过程的微观结构。研究人员发现，在非快速眼动睡眠的收缩瞳孔亚状态下，对最近经历的记忆回放以尖波波纹为主，而对先前记忆的回放则优先发生在扩张瞳孔亚状态。

在收缩瞳孔的非快速眼动睡眠期间，对尖波波纹的选择性闭环破坏会损害对最近记忆的回忆，而在扩张瞳孔的亚状态下，同样的操作没有行为影响。更强的外部兴奋性输入是收缩瞳孔亚状态的特征，而在扩张瞳孔亚状态下，更高的局部抑制募集更为突出。因此，非快速眼动睡眠的微观结构组织了记忆重放，先前的记忆和新的记忆在不同的子状态中被暂时隔离，并分别由局部和输入驱动机制支持。

总之，这一研究结果表明，大脑可以在睡眠期间复用不同的认知过程，以促进持续学习而不受干扰。

附：英文原文

Title: Sleep microstructure organizes memory replay

Author: Chang, Hongyu, Tang, Wenbo, Wulf, Annabella M., Nyasulu, Thokozile, Wolf, Madison E., Fernandez-Ruiz, Antonio, Oliva, Azahara

Issue&Volume: 2025-01-01

Abstract: Recently acquired memories are reactivated in the hippocampus during sleep, an initial step for their consolidation1,2,3. This process is concomitant with the hippocampal reactivation of previous memories4,5,6, posing the problem of how to prevent interference between older and recent, initially labile, memory traces. Theoretical work has suggested that consolidating multiple memories while minimizing interference can be achieved by randomly interleaving their reactivation7,8,9,10. An alternative is that a temporal microstructure of sleep can promote the reactivation of different types of memories during specific substates. Here, to test these two hypotheses, we developed a method to simultaneously record large hippocampal ensembles and monitor sleep dynamics through pupillometry in naturally sleeping mice. Oscillatory pupil fluctuations revealed a previously unknown microstructure of non-REM sleep-associated memory processes. We found that memory replay of recent experiences dominated in sharp-wave ripples during contracted pupil substates of non-REM sleep, whereas replay of previous memories preferentially occurred during dilated pupil substates. Selective closed-loop disruption of sharp-wave ripples during contracted pupil non-REM sleep impaired the recall of recent memories, whereas the same manipulation during dilated pupil substates had no behavioural effect. Stronger extrinsic excitatory inputs characterized the contracted pupil substate, whereas higher recruitment of local inhibition was prominent during dilated pupil substates. Thus, the microstructure of non-REM sleep organizes memory replay, with previous versus new memories being temporally segregated in different substates and supported by local and input-driven mechanisms, respectively. Our results suggest that the brain can multiplex distinct cognitive processes during sleep to facilitate continuous learning without interference.

DOI: 10.1038/s41586-024-08340-w

Source: https://www.nature.com/articles/s41586-024-08340-w