Elucidation of emotional regulation underlying metaplasticity during brain development

• Project/Area Number: 21591530
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Health Sciences University of Hokkaido
• Principal Investigator: MATSUMOTO Machiko 北海道医療大学, 薬学部, 准教授 (70229574)
• Co-Investigator(Kenkyū-buntansha): TOGASHI Hiroko 北海道医療大学, 薬学部, 教授 (20113590) ; 木村 真一 北海道医療大学, 薬学部, 講師 (90281287)
• Co-Investigator(Renkei-kenkyūsha): KIMURA Shin-ichi 北海道医療大学, 薬学部, 講師 (90281287)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 脳機能発達 / 幼児期ストレス / 神経可塑性 / 臨界期 / ERK活性 / 恐怖記憶 / セロトニン / メタ可塑性 / 幼若期ストレス / 心的外傷後ストレス

Research Abstract

The present study demonstrated that early postnatal stress caused extinction deficit in adult rats, in which "critical period" exists during brain development. This extinction deficit appears to be associated with dysfunction of hippocampal CA1 field and/or medial prefrontal cortex(mPFC), because synaptic potentiation and ERK activation induced by extinction processes, in a brain specific manner, did not occur in juvenile stress model rats. This impaired synaptic plasticity and suppressed ERK activity, in addition to behavioral deficit were ameliorated by pretreatment with a NMDA receptor agonist D-cycloserine. These results suggest that the different phenotypes in adulthood result from neurodevelopmental perturbations of neural circuits of emotional regulation that elicited by early life stress.

Research Products

• [Journal Article] Early postnatal stress alters extracellular s ignal-regulated kinase signaling in the corticoli mbic system modulating emotional circuitry in adult rats (2011)
  • Author(s): Ishikawa S, Saito Y, Yanagawa Y, Otani S, Hir aide S, Shimamura K, Matsumoto M, Togashi H.
  • Journal Title: Eur J Neuroscience Volume: 35 Pages: 135-145
  • Peer Reviewed
• [Journal Article] Serotonin_<1A> receptor-mediated synaptic response in the rat medial prefrontal cortex is altered by early life stress-in vivo and in vitro electrophysiological studies. (2011)
  • Author(s): Kimura S, Togashi H, Matsumoto M, Shiozawa T, Ishida J, Kano S, Ohashi A, Ishikawa S, Yamaguchi T, Yoshioka M, Shimamura K.
  • Journal Title: Jpn. J. Neuropsychopharmacol Volume: 31 Pages: 9-15
  • NAID: 10029093883
  • Peer Reviewed
• [Journal Article] Mechanisms underlying ketamine-induced synaptic depression in rat hippocampus-medial prefrontal cortex pathway (2011)
  • Author(s): Kamiyama H, Matsumoto M, Otani S, Kimura S, Shimamura K, Ishikawa S, Yanagawa Y, Togashi H.
  • Journal Title: Neuroscience Volume: 177 Pages: 159-169
  • Peer Reviewed
• [Journal Article] Adrenoceptor-mediated enhancement of interleukin-33 production by dendritic cells (2011)
  • Author(s): Yanagawa Y, Matsumoto M, Togashi H
  • Journal Title: Brain Behav Immun Volume: 25 Pages: 1427-1433
  • Peer Reviewed
• [Journal Article] Early postnatal stress alters extracellular signal-regulated kinase signaling in the corticolimbic system modulating emotional circuitry in adult rats (2011)
  • Author(s): Ishikawa S, Saito Y, Yanagawa Y, Otani S, Hiraide S, Shimamura K, Matsumoto M, Togashi H
  • Journal Title: Eur J Neurosci Volume: 35 Pages: 135-145
  • Peer Reviewed
• [Journal Article] Prostaglandin E(2) enhances IL-33 production by dendritic cells (2011)
  • Author(s): Yanagawa Y, Suzuki M, Matsumoto M, Togashi H
  • Journal Title: Immunol Lett Volume: 141 Pages: 55-60
  • Peer Reviewed
• [Journal Article] Enhanced dendritic cell antigen uptake via alpha2 adrenoceptor-mediated PI3K activation following brief exposure to noradrenaline (2010)
  • Author(s): Yanagawa Y, Matsumoto M, Togashi H.
  • Journal Title: J. Immunol Volume: 185 Pages: 5762-5768
  • Peer Reviewed
• [Journal Article] Diazepam-induced increases of synaptic efficacy in the hippocampal-medial prefrontal cortex pathway are associated with its anxiolytic-like effect in rats (2010)
  • Author(s): Shikanai H, Izumi T, Matsumoto M, Togashi H, Yamaguchi T, Yoshida T, Yoshioka M.
  • Journal Title: J. Pharmacol. Sci. Volume: 114 Pages: 341-346
  • Peer Reviewed
• [Journal Article] Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT_<1A> receptor function in adult rats (2010)
  • Author(s): Matsuzaki H, Izumi T, Horinouchi T, Boku S, Inoue T, Yamaguchi T, Yoshida T, Matsumoto M, Togashi H, Miwa S, Koyama T, Yoshioka M.
  • Journal Title: Psychopharmacology Volume: 214 Pages: 329-337
  • Peer Reviewed
• [Journal Article] Early stress exposure impairs synaptic potentiation in the rat medial prefrontal cortex underlying contextual fear extinction (2010)
  • Author(s): Judo C, Matsumoto M, Yamazaki D, Hiraide S, Yanagawa Y, Kimura S, Shimamura K, Togashi H.
  • Journal Title: Neuroscience Volume: 169 Pages: 1705-1714
  • Peer Reviewed
• [Journal Article] Early stress exposure impairs synaptic potentiation in the rat medial prefrontal cortex underlying contextual fear extinction. (2010)
  • Author(s): Judo C, Matsumoto M, et al.
  • Journal Title: Neuroscience Volume: 169 Pages: 1705-1714
  • Peer Reviewed
• [Journal Article] Juvenile stress attenuates the dorsal hippocampal postsynaptic 5-HT(1A) receptor function in adult rats. (2010)
  • Author(s): Matsuzaki H, Izumi T, et al.
  • Journal Title: Psychopharmacology(Berl) Volume: 214 Pages: 329-337
  • Peer Reviewed
• [Journal Article] Enhanced dendritic cell antigen-uptake via α_2 adrenoceptor-mediated PI3K activation following brief exposure to noradrenaline. (2010)
  • Author(s): Yanagawa Y, Matsumoto M, et al
  • Journal Title: Journal of Immunology. Volume: 15 Pages: 5762-5768
  • Peer Reviewed
• [Journal Article] Early postnatal stress and neural circuit underlying emotional regulation (2009)
  • Author(s): Matsumoto M, Yoshioka M, Togashi H.
  • Journal Title: International review of neurobiology Volume: 85 Pages: 95-107
• [Journal Article] Corticotropin releasing factor enhances attentional function as assessed by the five-choice serial reaction time task in rats (2009)
  • Author(s): Ohmura Y, Yamaguchi T, Futami Y, Togashi H, Izumi T, Matsumoto M, Yoshid T, Yoshioka M.
  • Journal Title: Behav Brain Res Volume: 198 Pages: 429-433
  • Peer Reviewed
• [Journal Article] Early postnatal stress affects 5-HT_<1A> receptor function in the medial prefrontal cortex in adult rats (2009)
  • Author(s): Matsuzaki H, Izumi T, Matsumoto M, Togashi H, Yamaguchi T, Yoshida T, Watanabe M, Yoshioka M.
  • Journal Title: Eur J Parmacol Volume: 615 Pages: 76-82
  • Peer Reviewed
• [Journal Article] Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats (2009)
  • Author(s): Hirata R, Matsumoto M, Judo C, Yamaguchi T, Izumi T, Yoshioka M, Togashi H.
  • Journal Title: Synapse Volume: 63 Pages: 549-56
  • Peer Reviewed
• [Journal Article] Alteration of synaptic transmission in the hippocampal-mPFC pathway during extinction trials of context-dependent fear memory in juvenile rat stress models (2009)
  • Author(s): Koseki H, Matsumoto M, Togashi H, Miura Y, Fukushima K, Yoshioka M.
  • Journal Title: Synapse Volume: 63 Pages: 805-13
  • Peer Reviewed
• [Journal Article] Alteration of synaptic transmission in the hippocampal-mPFC pathway during extinction trials of context-dependent fear memory in juvenile rat stress models (2009)
  • Author(s): Koseki H., Matsumoto M., et al.
  • Journal Title: Synapse 63 Pages: 805-813
  • Peer Reviewed
• [Journal Article] Possible relationship between the stress-induced synaptic response and metaplasticity in the hippocampal CA1 field of freely moving rats. (2009)
  • Author(s): Hirata R, Matsumoto M, et al.
  • Journal Title: Synapse 83 Pages: 549-556
  • Peer Reviewed
• [Journal Article] Early postnatal stress affects 5-HT1A receptor function in the medial prefrontal cortex in adult rats. (2009)
  • Author(s): Matsuzaki H, Izumi T, Matsumoto M, et al.
  • Journal Title: European Journal of Pharmacology 615 Pages: 76-82
  • NAID: 120001452160
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Matsumoto M, et al.
  • Journal Title: Early postnatal stress and neural circuit underlying emotional regulation. International Review of Neurobiology(Academid Press) Pages: 95-107
• [Presentation] ストレス下の海馬シナプス応答に対する扁桃体の調節と幼若期ストレスの影響 (2011)
  • Author(s): 平出幸子、松本真知子、富樫廣子, 他
  • Organizer: 第41回日本神経精神薬理学会
  • Place of Presentation: 東京
  • Year and Date: 2011-10-29
• [Presentation] 幼若期ストレスによる神経可塑的変化と精神疾患との関連性 (2011)
  • Author(s): 松本真知子、富樫廣子
  • Organizer: 第34回日本神経科学大会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2011-09-29
• [Presentation] 情動応答におけるToll-like receptor (TLR)の役割 (2011)
  • Author(s): 久保靖憲、柳川芳毅、松本眞知子、平出幸子、富樫廣子
  • Organizer: 第25回北海道薬物作用談話会
  • Place of Presentation: 札幌
  • Year and Date: 2011-07-30
• [Presentation] Neural plasticity and developmental stress (2011)
  • Author(s): 松本真知子、富樫廣子
  • Organizer: 日・伊合同国際交流学術セミナー
  • Place of Presentation: 仙台
  • Year and Date: 2011-06-02
• [Presentation] SHRSPの恐怖ストレスに対する皮質前頭前野シナプス応答 (2011)
  • Author(s): 平出幸子、松本真知子、柳川芳毅、山口拓、吉岡充弘、富樫廣子
  • Organizer: 第47回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 中枢神経系からみたSHR亜系と表現型の多様性」皮質-辺縁系シナプス応答とSHRSP/Ezo:第47回高血圧関連疾患モデル学会学術総会 (2011)
  • Author(s): 木村真一、松本真知子、富樫廣子、島村佳一:シンポジウム
  • Organizer: 第47回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Early postnatal stress alters extracellular signal-regulated kinase signaling in the corticolimbic system underlying emotional regulation in adult rats (2010)
  • Author(s): Ishikawa S, Matsumoto M, Togashi H., et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: SanDiego
  • Year and Date: 2010-11-16
• [Presentation] Early postnatal stress alters extracellular signal-regulated kinase signaling in the corticolimbic system underlying emotional regulation in adult rats (2010)
  • Author(s): Ishikawa S, Matsumoto M, et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: San Diego Convention center(U.S.A)
  • Year and Date: 2010-11-16
• [Presentation] Context-dependent fear memory deficit accompanied with synaptic impairment in the rat medial prefrontal cortex (2010)
  • Author(s): Hiraide Y, Matsumoto M Togashi H., et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: SanDiego
  • Year and Date: 2010-11-15
• [Presentation] Impaired fear extinction by exposure to early postnatal stress : evidence of altered neuronal processing in the rat hippocampus and medial prefrontal cortex network (2010)
  • Author(s): Saito Y, Matsumoto M, Togashi H., et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: SanDiego
  • Year and Date: 2010-11-15
• [Presentation] Impaired fear extinction by exposure to early postnatal stress : evidence of altered neuronal processing in the rat hippocampus and medial prefrontal cortex network. (2010)
  • Author(s): Saito Y, Matsumoto M, et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: San Diego Convention center(U.S.A)
  • Year and Date: 2010-11-15
• [Presentation] Context-dependent fear memory deficit accompanied with synaptic impairment in the rat medial prefrontal cortex. (2010)
  • Author(s): Hiraide Y, Matsumoto M, et al.
  • Organizer: Society for Neuroscience 40^<th> annual meeting
  • Place of Presentation: San Diego Convention center(U.S.A)
  • Year and Date: 2010-11-15
• [Presentation] Early life stress and neural circuits underlying fear extinction in rats : translational approaches for psychotherapy of posttraumatic stress disorder (2010)
  • Author(s): Matsumoto M, Togashi H.
  • Organizer: XXVII CINP World Congress
  • Place of Presentation: 香港
  • Year and Date: 2010-06-10
• [Presentation] Early life stress and neural circuits underlying fear extinction in rats : translational approaches for psychotherapy of posttraumatic stress Disorder (2010)
  • Author(s): Matsumoto M, Togashi H
  • Organizer: XXVII CINP World Congress
  • Place of Presentation: Hong-Kong Convention center(China)
  • Year and Date: 2010-06-10
• [Presentation] Ketamine-induced cortical dysfunction involved in dopaminergic and GABAergic mechanisms in rats (2010)
  • Author(s): Togashi H, Matsumoto M, et al.
  • Organizer: XXVII CINP World Congress
  • Place of Presentation: 香港
  • Year and Date: 2010-06-07
• [Presentation] Ketamine-induced cortical dysfunction involved in dopaminergic and GABAergic mechanisms in rats (2010)
  • Author(s): Togashi H, Matsumoto M, et al.
  • Organizer: XXVII CINP World Congress
  • Place of Presentation: Hong-Kong Convention center(China)
  • Year and Date: 2010-06-07
• [Presentation] Early postnatal stress alters fear extinction-associated prefrontal synaptic plasticity of adult rats (2009)
  • Author(s): 松本真知子, 他
  • Organizer: 第32回日本神経科学学会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2009-09-17
• [Presentation] Early postnatal stress : Impact on neural circuits and relevance to psychophysiology (2009)
  • Author(s): 松本真知子, 他
  • Organizer: 9^<th> World Congress of Biological Psychiatry
  • Place of Presentation: フランス(パリ)
  • Year and Date: 2009-06-28
• [Book] Early postnatal stress and emotional Vulnerability : Focus on neural circuits underlying fear memory in rats.(L. Sher and A. Vilens, eds.) (2010)
  • Author(s): Matsumoto M, Togashi H.
  • Publisher: Nova Science Publishers
• [Book] Neurobiology of Post-traumatic Stress Disorder : Early postnatal stress and emotional vulnerability : Focus on Neural circuits underlying fear memory in rats (2010)
  • Author(s): Matsumoto M, Togashi H
  • Publisher: Nova Science Publishers, Inc.(New York)