| Title: | Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories |
| Authors: | Nomura, Hiroshi Browse this author →KAKEN DB |
| Mizuta, Hiroto Browse this author |
| Norimoto, Hiroaki Browse this author |
| Masuda, Fumitaka Browse this author |
| Miura, Yuki Browse this author |
| Kubo, Ayame Browse this author |
| Kojima, Hiroto Browse this author |
| Ashizuka, Aoi Browse this author |
| Matsukawa, Noriko Browse this author |
| Baraki, Zohal Browse this author |
| Hitora-Imamura, Natsuko Browse this author |
| Nakayama, Daisuke Browse this author |
| Ishikawa, Tomoe Browse this author |
| Okada, Mami Browse this author |
| Orita, Ken Browse this author |
| Saito, Ryoki Browse this author |
| Yamauchi, Naoki Browse this author |
| Sano, Yamato Browse this author |
| Kusuhara, Hiroyuki Browse this author |
| Minami, Masabumi Browse this author →KAKEN DB |
| Takahashi, Hidehiko Browse this author |
| Ikegaya, Yuji Browse this author |
| Keywords: | Histamine H-3 receptor |
| Memory recovery |
| Object recognition memory |
| Perirhinal cortex |
| Retrieval |
| Stochastic resonance |
| Issue Date: | 1-Aug-2019 |
| Publisher: | Elsevier |
| Journal Title: | Biological psychiatry |
| Volume: | 86 |
| Issue: | 3 |
| Start Page: | 230 |
| End Page: | 239 |
| Publisher DOI: | 10.1016/j.biopsych.2018.11.009 |
| Abstract: | BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H-3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H-3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H-3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H-2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H-3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrains. |
| Rights: | ©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/79001 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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