Department of Biology, Pennsylvania State University, University Park, PA, 16802, USA.
Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
Neuropsychopharmacology. 2023 Nov;48(12):1789-1797. doi: 10.1038/s41386-023-01616-1. Epub 2023 Jun 1.
The circadian system influences many different biological processes, including memory performance. While the suprachiasmatic nucleus (SCN) functions as the brain's central pacemaker, downstream "satellite clocks" may also regulate local functions based on the time of day. Within the dorsal hippocampus (DH), for example, local molecular oscillations may contribute to time-of-day effects on memory. Here, we used the hippocampus-dependent Object Location Memory task to determine how memory is regulated across the day/night cycle in mice. First, we systematically determined which phase of memory (acquisition, consolidation, or retrieval) is modulated across the 24 h day. We found that mice show better long-term memory performance during the day than at night, an effect that was specifically attributed to diurnal changes in memory consolidation, as neither memory acquisition nor memory retrieval fluctuated across the day/night cycle. Using RNA-sequencing we identified the circadian clock gene Period1 (Per1) as a key mechanism capable of supporting this diurnal fluctuation in memory consolidation, as learning-induced Per1 oscillates in tandem with memory performance in the hippocampus. We then show that local knockdown of Per1 within the DH impairs spatial memory without affecting either the circadian rhythm or sleep behavior. Thus, Per1 may independently function within the DH to regulate memory in addition to its known role in regulating the circadian system within the SCN. Per1 may therefore exert local diurnal control over memory consolidation within the DH.
昼夜节律系统影响许多不同的生物过程，包括记忆表现。虽然视交叉上核（SCN）是大脑的中央起搏器，但下游的“卫星钟”也可能根据时间来调节局部功能。例如，在背侧海马体（DH）中，局部分子振荡可能有助于记忆的时间效应。在这里，我们使用海马体依赖性物体位置记忆任务来确定记忆在小鼠的昼夜周期中是如何被调节的。首先，我们系统地确定了记忆的哪个阶段（获取、巩固或检索）在 24 小时周期内被调节。我们发现，与夜间相比，小鼠在白天表现出更好的长期记忆能力，这种效应专门归因于记忆巩固的昼夜变化，因为记忆获取和检索都没有随昼夜周期波动。使用 RNA 测序，我们确定了节律钟基因 Period1（Per1）是支持记忆巩固这种昼夜波动的关键机制，因为学习诱导的 Per1 与海马体中的记忆表现同步振荡。然后，我们表明，DH 内 Per1 的局部敲低会损害空间记忆，而不会影响昼夜节律或睡眠行为。因此，除了其在 SCN 中调节昼夜节律系统的已知作用外，Per1 可能在 DH 内独立发挥作用以调节记忆。因此，Per1 可能在 DH 内对记忆巩固进行本地的昼夜控制。
