Balendran Vinodh, Liu Jiyang, Wu Katelin, Aton Sara J
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48019.
bioRxiv. 2025 Aug 28:2025.08.22.671839. doi: 10.1101/2025.08.22.671839.
Brief sleep loss alters cognition and the activity and synaptic structures of both principal neurons and interneurons in hippocampus. However, although sleep-dependent coordination of activity between hippocampus and neocortex is essential for memory consolidation, much less is known about how sleep loss affects neocortical input to hippocampus, or excitatory-inhibitory balance within neocortical structures. We aimed to test how the synaptic structures of SST+ interneurons in lateral and medial entorhinal cortex (LEC and MEC), which are the major neocortical input to hippocampus, are affected by brief sleep disruption in the hours following learning.
We used Brainbow 3.0 to label SST+ interneurons in the LEC or MEC of male transgenic mice. We then compared synaptic structures in labeled neurons after single trial contextual fear conditioning (CFC) followed by either a 6-h period of sleep, or gentle handling sleep deprivation (SD), focusing on cortical layers providing input to hippocampus.
Dendritic spine density among EC SST+ interneurons was altered in a subregion-specific manner, with dramatic alterations in dendritic spine type distributions and reductions in spine size in LEC, but not MEC, after post-CFC SD.
Our data suggest that the synaptic connectivity of SST+ interneurons is significantly reduced in LEC when learning is followed by sleep disruption. This suggests that post-learning sleep loss disrupts hippocampus-dependent memory processing in part through altered excitatory-inhibitory balance in neocortical structures providing input to hippocampus. They also provide more mechanistic insight into sleep's role in coordinating neocortical-hippocampal communication in the context of memory consolidation.
短期睡眠不足会改变认知以及海马体中主要神经元和中间神经元的活动及突触结构。然而，尽管海马体和新皮层之间依赖睡眠的活动协调对于记忆巩固至关重要，但对于睡眠不足如何影响新皮层对海马体的输入，或新皮层结构内的兴奋性 - 抑制性平衡，我们所知甚少。我们旨在测试学习后数小时内的短期睡眠中断如何影响外侧和内侧内嗅皮层（LEC和MEC）中SST + 中间神经元的突触结构，这两个区域是海马体的主要新皮层输入源。
我们使用Brainbow 3.0标记雄性转基因小鼠LEC或MEC中的SST + 中间神经元。然后，在单次试验情境恐惧条件反射（CFC）后，比较标记神经元在经历6小时睡眠或轻度处理睡眠剥夺（SD）后的突触结构，重点关注向海马体提供输入的皮层层。
CFC后SD处理后，EC SST + 中间神经元的树突棘密度以亚区域特异性方式改变，LEC中树突棘类型分布发生显著变化且棘突尺寸减小，而MEC中未出现此现象。
我们的数据表明，学习后睡眠中断时，LEC中SST + 中间神经元的突触连接性显著降低。这表明学习后睡眠不足部分通过改变向海马体提供输入的新皮层结构中的兴奋性 - 抑制性平衡，破坏了依赖海马体的记忆处理。它们还为睡眠在记忆巩固过程中协调新皮层 - 海马体通信的作用提供了更多的机制性见解。
