Department of Physiology, Third Military Medical University, Chongqing, China.
Department of Neurosurgery, General Hospital of Chinese PLA Central Theater Command, Wuhan, China.
Nat Commun. 2024 Oct 25;15(1):9231. doi: 10.1038/s41467-024-53522-9.
During non-rapid eye movement (NREM) sleep, neural ensembles in the entorhinal-hippocampal circuit responsible for encoding recent memories undergo reactivation to facilitate the process of memory consolidation. This reactivation is widely acknowledged as pivotal for the formation of stable memory and its impairment is closely associated with memory dysfunction. To date, the neural mechanisms driving the reactivation of neural ensembles during NREM sleep remain poorly understood. Here, we show that the neural ensembles in the medial entorhinal cortex (MEC) that encode spatial experiences exhibit reactivation during NREM sleep. Notably, this reactivation consistently coincides with isolated theta waves. In addition, we found that the nucleus reuniens (RE) in the midline thalamus exhibits typical theta waves during NREM sleep, which are highly synchronized with those occurring in the MEC in male mice. Closed-loop optogenetic inhibition of the RE-MEC pathway specifically suppressed these isolated theta waves, resulting in impaired reactivation and compromised memory consolidation following a spatial memory task in male mice. The findings suggest that theta waves originating from the ventral midline thalamus play a role in initiating memory reactivation and consolidation during sleep.
在非快速眼动 (NREM) 睡眠期间，负责编码近期记忆的内嗅皮层-海马回路中的神经集合体经历再激活，以促进记忆巩固的过程。这种再激活被广泛认为是形成稳定记忆的关键，其损伤与记忆功能障碍密切相关。迄今为止，驱动 NREM 睡眠期间神经集合体再激活的神经机制仍知之甚少。在这里，我们表明编码空间体验的内侧内嗅皮层 (MEC) 中的神经集合体在 NREM 睡眠期间会发生再激活。值得注意的是，这种再激活与孤立的 theta 波一致。此外，我们发现中脑中线丘脑的 reuniens 核 (RE) 在 NREM 睡眠期间会出现典型的 theta 波，这些波与雄性小鼠 MEC 中的 theta 波高度同步。对 RE-MEC 通路进行闭环光遗传学抑制特异性抑制了这些孤立的 theta 波，导致雄性小鼠在进行空间记忆任务后，再激活和记忆巩固受损。这些发现表明，来自腹侧中线丘脑的 theta 波在睡眠期间启动记忆再激活和巩固过程中发挥作用。
