Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories

Hiroshi Nomura, Hiroto Mizuta, Hiroaki Norimoto, Fumitaka Masuda, Yuki Miura, A. Kubo, Hiroto Kojima, Aoi Ashizuka, Noriko Matsukawa, Z. Baraki, Natsuko Hitora-Imamura, Daisuke Nakayama, T. Ishikawa, Mami Okada, Ken Orita, R. Saito, N. Yamauchi, Yamato Sano, Hiroyuki Kusuhara, Masabumi MinamiHidehiko Takahashi, Yuji Ikegaya

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 H3 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 H3 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 H3 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 H2 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 H3 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 engrams.

Original languageEnglish
Pages (from-to)230-239
Number of pages10
JournalBiological Psychiatry
Volume86
Issue number3
DOIs
Publication statusPublished - 2019 Aug 1
Externally publishedYes

Fingerprint

Histamine
Long-Term Memory
Betahistine
Histamine H3 Receptors
Histamine Agonists
thioperamide
Histamine Release
Learning
Histamine H2 Receptors
Histamine Antagonists
Therapeutics
Perirhinal Cortex
Cross-Over Studies
Healthy Volunteers
Up-Regulation
Central Nervous System
Placebos
Clinical Trials
Calcium
Neurons

Keywords

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

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Nomura, H., Mizuta, H., Norimoto, H., Masuda, F., Miura, Y., Kubo, A., ... Ikegaya, Y. (2019). Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories. Biological Psychiatry, 86(3), 230-239. https://doi.org/10.1016/j.biopsych.2018.11.009

Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories. / Nomura, Hiroshi; Mizuta, Hiroto; Norimoto, Hiroaki; Masuda, Fumitaka; Miura, Yuki; Kubo, A.; Kojima, Hiroto; Ashizuka, Aoi; Matsukawa, Noriko; Baraki, Z.; Hitora-Imamura, Natsuko; Nakayama, Daisuke; Ishikawa, T.; Okada, Mami; Orita, Ken; Saito, R.; Yamauchi, N.; Sano, Yamato; Kusuhara, Hiroyuki; Minami, Masabumi; Takahashi, Hidehiko; Ikegaya, Yuji.

In: Biological Psychiatry, Vol. 86, No. 3, 01.08.2019, p. 230-239.

Research output: Contribution to journalArticle

Nomura, H, Mizuta, H, Norimoto, H, Masuda, F, Miura, Y, Kubo, A, Kojima, H, Ashizuka, A, Matsukawa, N, Baraki, Z, Hitora-Imamura, N, Nakayama, D, Ishikawa, T, Okada, M, Orita, K, Saito, R, Yamauchi, N, Sano, Y, Kusuhara, H, Minami, M, Takahashi, H & Ikegaya, Y 2019, 'Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories', Biological Psychiatry, vol. 86, no. 3, pp. 230-239. https://doi.org/10.1016/j.biopsych.2018.11.009
Nomura, Hiroshi ; Mizuta, Hiroto ; Norimoto, Hiroaki ; Masuda, Fumitaka ; Miura, Yuki ; Kubo, A. ; Kojima, Hiroto ; Ashizuka, Aoi ; Matsukawa, Noriko ; Baraki, Z. ; Hitora-Imamura, Natsuko ; Nakayama, Daisuke ; Ishikawa, T. ; Okada, Mami ; Orita, Ken ; Saito, R. ; Yamauchi, N. ; Sano, Yamato ; Kusuhara, Hiroyuki ; Minami, Masabumi ; Takahashi, Hidehiko ; Ikegaya, Yuji. / Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories. In: Biological Psychiatry. 2019 ; Vol. 86, No. 3. pp. 230-239.
@article{0282d590abc94d709198ea32a19960e3,
title = "Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories",
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 H3 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 H3 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 H3 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 H2 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 H3 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 engrams.",
keywords = "Histamine H receptor, Memory recovery, Object recognition memory, Perirhinal cortex, Retrieval, Stochastic resonance",
author = "Hiroshi Nomura and Hiroto Mizuta and Hiroaki Norimoto and Fumitaka Masuda and Yuki Miura and A. Kubo and Hiroto Kojima and Aoi Ashizuka and Noriko Matsukawa and Z. Baraki and Natsuko Hitora-Imamura and Daisuke Nakayama and T. Ishikawa and Mami Okada and Ken Orita and R. Saito and N. Yamauchi and Yamato Sano and Hiroyuki Kusuhara and Masabumi Minami and Hidehiko Takahashi and Yuji Ikegaya",
year = "2019",
month = "8",
day = "1",
doi = "10.1016/j.biopsych.2018.11.009",
language = "English",
volume = "86",
pages = "230--239",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories

AU - Nomura, Hiroshi

AU - Mizuta, Hiroto

AU - Norimoto, Hiroaki

AU - Masuda, Fumitaka

AU - Miura, Yuki

AU - Kubo, A.

AU - Kojima, Hiroto

AU - Ashizuka, Aoi

AU - Matsukawa, Noriko

AU - Baraki, Z.

AU - Hitora-Imamura, Natsuko

AU - Nakayama, Daisuke

AU - Ishikawa, T.

AU - Okada, Mami

AU - Orita, Ken

AU - Saito, R.

AU - Yamauchi, N.

AU - Sano, Yamato

AU - Kusuhara, Hiroyuki

AU - Minami, Masabumi

AU - Takahashi, Hidehiko

AU - Ikegaya, Yuji

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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 H3 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 H3 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 H3 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 H2 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 H3 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 engrams.

AB - 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 H3 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 H3 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 H3 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 H2 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 H3 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 engrams.

KW - Histamine H receptor

KW - Memory recovery

KW - Object recognition memory

KW - Perirhinal cortex

KW - Retrieval

KW - Stochastic resonance

UR - http://www.scopus.com/inward/record.url?scp=85062890693&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062890693&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2018.11.009

DO - 10.1016/j.biopsych.2018.11.009

M3 - Article

C2 - 30635130

AN - SCOPUS:85062890693

VL - 86

SP - 230

EP - 239

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 3

ER -