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Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories

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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
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
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 野村 洋

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