Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors

作者：Lizhu Jiang, Liping Wang, Yan Yin, Mengke Huo, Chao Liu, Qi‐Xin Zhou, Dafu Yu, Lin Xu, Rongrong Mao · 发表于：Frontiers in Molecular Neuroscience · 年份：2020 · DOI：10.3389/fnmol.2019.00317 · 被引用次数：11 · 研究领域：Receptor Mechanisms and Signaling、Memory and Neural Mechanisms、Neuroscience and Neuropharmacology Research

Spaced training is robustly superior to massed training, which is a well-documented phenomenon in human and animal. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting via decreasing hippocampal Rac1 activity. Here, using contextual fear conditioning in rat, we found that spaced but not massed training increased hippocampal 5-HT2A receptors expression. Furthermore, hippocampal administration of 5-HT2A receptor antagonist MDL11939 before spaced training blocked the enhanced memory, while hippocampal administration of 5-HT2A receptor agonist TCB-2 before massed training promoted the memory. Moreover, MDL11939 activated hippocampal Rac1, while TCB-2 decreased hippocampal Rac1 activity in naïve rats. These results indicated the possibility of interaction between 5-HT2A receptors and Rac1, which was demonstrated by the Co-immunoprecipitation experiments. Our study firstly demonstrates that activation of hippocampal 5-HT2A is a mechanism underlying the spacing effect, and forgetting related molecular Rac1 is engaged in this process through interacting with 5-HT2A receptors, which suggest a promising strategy to modulate abnormal learning in cognitive disorders.