Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories

• Nomura, Hiroshi

• Mizuta, Hiroto

• Norimoto, Hiroaki

• Masuda, Fumitaka

• Miura, Yuki

• Kubo, Ayame

• Kojima, Hiroto

• Ashizuka, Aoi

• Matsukawa, Noriko

• Baraki, Zohal

• Hitora-Imamura, Natsuko

• Nakayama, Daisuke

• Ishikawa, Tomoe

• Okada, Mami

• Orita, Ken

• Saito, Ryoki

• Yamauchi, Naoki

• Sano, Yamato

• Kusuhara, Hiroyuki

• Minami, Masabumi

• Takahashi, Hidehiko

• Ikegaya, Yuji

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.

Journal

• Biological psychiatry

  Biological psychiatry 86 (3), 230-239, 2019-08-01

  Elsevier

Keywords

• Histamine H-3 receptor
• Memory recovery
• Object recognition memory
• Perirhinal cortex
• Retrieval
• Stochastic resonance

Details

• CRID: 1050285299903626752
• NII Article ID: 120006876277
• HANDLE: 2115/79001
• ISSN: 00063223
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles