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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-01-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00317/full |
| _version_ | 1818159485318856704 |
|---|---|
| author | Lizhu Jiang Lizhu Jiang Lizhu Jiang Liping Wang Yan Yin Mengke Huo Chao Liu Chao Liu Qixin Zhou Dafu Yu Lin Xu Lin Xu Rongrong Mao |
| author_facet | Lizhu Jiang Lizhu Jiang Lizhu Jiang Liping Wang Yan Yin Mengke Huo Chao Liu Chao Liu Qixin Zhou Dafu Yu Lin Xu Lin Xu Rongrong Mao |
| author_sort | Lizhu Jiang |
| collection | DOAJ |
| description | 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 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 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. |
| first_indexed | 2024-12-11T15:46:44Z |
| format | Article |
| id | doaj.art-5aff3c8e8db04f4c9980d2c9cc39e6d0 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-11T15:46:44Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-5aff3c8e8db04f4c9980d2c9cc39e6d02022-12-22T00:59:41ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-01-011210.3389/fnmol.2019.00317482700Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A ReceptorsLizhu Jiang0Lizhu Jiang1Lizhu Jiang2Liping Wang3Yan Yin4Mengke Huo5Chao Liu6Chao Liu7Qixin Zhou8Dafu Yu9Lin Xu10Lin Xu11Rongrong Mao12Department of Neuropsychopathy, Clinical Medical School, Dali University, Dali, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, ChinaDepartment of Central Laboratory, The Third People’s Hospital of Yunnan Province, Kunming, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, ChinaDepartment of Central Laboratory, The Third People’s Hospital of Yunnan Province, Kunming, ChinaDepartment of Neuropsychopathy, Clinical Medical School, Dali University, Dali, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, ChinaDepartment of Nuclear Medicine, The First People’s Hospital of Yunnan Province, Kunming, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, ChinaKey Lab of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing, ChinaDepartment of Pathology and Pathophysiology, School of Basic Medical Science, Kunming Medical University, Kunming, ChinaSpaced 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 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 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.https://www.frontiersin.org/article/10.3389/fnmol.2019.00317/fullspacing effect5-HT2A receptorRac1hippocampuscontextual fear memory |
| spellingShingle | Lizhu Jiang Lizhu Jiang Lizhu Jiang Liping Wang Yan Yin Mengke Huo Chao Liu Chao Liu Qixin Zhou Dafu Yu Lin Xu Lin Xu Rongrong Mao Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors Frontiers in Molecular Neuroscience spacing effect 5-HT2A receptor Rac1 hippocampus contextual fear memory |
| title | Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors |
| title_full | Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors |
| title_fullStr | Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors |
| title_full_unstemmed | Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors |
| title_short | Spaced Training Enhances Contextual Fear Memory via Activating Hippocampal 5-HT2A Receptors |
| title_sort | spaced training enhances contextual fear memory via activating hippocampal 5 ht2a receptors |
| topic | spacing effect 5-HT2A receptor Rac1 hippocampus contextual fear memory |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00317/full |
| work_keys_str_mv | AT lizhujiang spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT lizhujiang spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT lizhujiang spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT lipingwang spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT yanyin spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT mengkehuo spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT chaoliu spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT chaoliu spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT qixinzhou spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT dafuyu spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT linxu spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT linxu spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors AT rongrongmao spacedtrainingenhancescontextualfearmemoryviaactivatinghippocampal5ht2areceptors |