Department of Neuroscience, Ohio State University, Columbus, OH 43210, USA.
Neural Plast. 2018 Feb 8;2018:7292540. doi: 10.1155/2018/7292540. eCollection 2018.
Circadian modulation of learning and memory efficiency is an evolutionarily conserved phenomenon, occurring in organisms ranging from invertebrates to higher mammalian species, including humans. While the suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master mammalian pacemaker, recent evidence suggests that forebrain regions, including the hippocampus, exhibit oscillatory capacity. This finding, as well as work on the cellular signaling events that underlie learning and memory, has opened promising new avenues of investigation into the precise cellular, molecular, and circuit-based mechanisms by which clock timing impacts plasticity and cognition. In this review, we examine the complex molecular relationship between clock timing and memory, with a focus on hippocampal-dependent tasks. We evaluate how the dysregulation of circadian timing, both at the level of the SCN and at the level of ancillary forebrain clocks, affects learning and memory. Further, we discuss experimentally validated intracellular signaling pathways (e.g., ERK/MAPK and GSK3) and potential cellular signaling mechanisms by which the clock affects learning and memory formation. Finally, we examine how long-term potentiation (LTP), a synaptic process critical to the establishment of several forms of memory, is regulated by clock-gated processes.
昼夜节律对学习和记忆效率的调节是一种进化上保守的现象，发生在从无脊椎动物到高等哺乳动物物种的生物体中，包括人类。虽然下丘脑的视交叉上核（SCN）是哺乳动物的主生物钟，但最近的证据表明，包括海马体在内的前脑区域具有振荡能力。这一发现以及对学习和记忆基础的细胞信号事件的研究，为深入研究时钟计时如何影响可塑性和认知提供了有希望的新途径，其涉及精确的细胞、分子和基于电路的机制。在这篇综述中，我们研究了时钟计时与记忆之间复杂的分子关系，重点关注海马体依赖性任务。我们评估了生物钟的失调，无论是在 SCN 水平还是在辅助前脑生物钟水平，如何影响学习和记忆。此外，我们还讨论了经过实验验证的细胞内信号通路（例如 ERK/MAPK 和 GSK3）以及时钟影响学习和记忆形成的潜在细胞信号机制。最后，我们研究了长时程增强（LTP），即建立几种形式记忆的关键突触过程，是如何受时钟门控过程调节的。
