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

Spaced training is robustly superior to massed training, which is a well-documented phenomenon in humans and animals. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting...

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Published in:Frontiers in molecular neuroscience 2020-01, Vol.12, p.317-317
Main Authors: Jiang, Lizhu, Wang, Liping, Yin, Yan, Huo, Mengke, Liu, Chao, Zhou, Qixin, Yu, Dafu, Xu, Lin, Mao, Rongrong
Format: Article
Language:English
Subjects:
5-HT2A receptor
Cognitive ability
contextual fear memory
Fear conditioning
Hippocampus
Immunoprecipitation
Investigations
Memory
Neuroscience
Phosphatase
Rac1
Rac1 protein
Serotonin S2 receptors
spacing effect
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Summary:Spaced training is robustly superior to massed training, which is a well-documented phenomenon in humans and animals. However, the mechanisms underlying the spacing effect still remain unclear. We have reported previously that spacing training exerts memory-enhancing effects by inhibiting forgetting 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 co-immunoprecipitation experiments. Our study first 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.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2019.00317