Elucidation of physiological significance of newly discovered CRH release pathway and its relationship with known HPA axis

• Project/Area Number: 17H04025
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: 福田 敦夫 浜松医科大学, 医学部, 教授 (50254272)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Granted (Fiscal Year 2020)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2020: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: 摂食 / 室傍核 / HPA Axis / CRH / 弓状核 / HPA axis

Outline of Annual Research Achievements

１．AgRP細胞からCRH細胞終末へGABA作動性興奮性投射の証明：CRH Cre :: AgRP CreマウスのPVNにCre依存性にGCaMP6fを発現するAAVを、ARCにDREADDを発現するAAVをそれぞれインジェクションし、CRHニューロンにGCaMP6f、AgRPニューロンにDREADDを発現するマウスを作成した。弓状核スライス標本を作成しパッチクランプを行い、CNO投与によりシナプス伝達を遮断したAgRPニューロン細胞体で興奮が起こることを確認した。しかし、AgRPニューロン同士のネットワークにより、広範な投与では興奮が起こりにくいことも分かった。したがってインビボでのCNOの効果判定には注意が必要である。さらに、CRHニューロン終末ではAgRPニューロンの投射がみられることを正中隆起の免疫組織染色を行い確認したが、AgRPは正中隆起末では多くなかった。
２．AgRP細胞からCRH細胞終末へGABA作動性興奮性投射の生理学的意義の検討：AgRP Cre :: GAD67 floxマウス、およびCRHニューロンでNKCC1を欠失させたCRH Cre :: NKCC1 floxマウスを作成した。
３．胎仔における既知HPA軸と新規HPA軸の機能的発達過程の解明： CRH抗体とVGAT抗体を用いて胎仔―出生直後―新生仔期の正中隆起におけるCRH投射とGABA投射の有無を検討した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

CNO投与によりAgRPニューロン細胞体で興奮が起こることを確認したが、広範な投与では興奮が起こりにくいことも分かったので、今後インビボでのCNOの効果判定には注意が必要である。
CRHニューロン終末へのAgRPニューロンの投射があることは確認できたが、AgRPは軸索終末までは至っていない印象であった。AgRPニューロンの伝達物質はGABAと考えているので矛盾はないが、今後は電顕を用いてで両ニューロンの軸索終末でのコンタクトを証明する必要がある。
AgRP ニューロンでGABAを減少させたAgRP Cre :: GAD67 floxマウス、CRHニューロンでNKCC1を欠失させたCRH Cre :: NKCC1 floxマウスを作成したので、今後は、60%食餌制限ストレスを10日間負荷した後のCORT分泌を野生型と比較することができる。
胎仔―新生仔期の正中隆起におけるCRH投射とGABA投射の完成時期を同定するために例数を増やす必要がある。

Strategy for Future Research Activity

１．AgRP細胞からCRH細胞終末へGABA作動性興奮性投射の証明：CRHニューロン終末にAgRPニューロンの投射がみられることを正中隆起の免疫電子顕微鏡で証明する。CRH-GCaMP6f::AgRP-DREADDマウスを用い、スライス標本を作成し、CNO投与によりCRHニューロン終末で細胞内Ca2+上昇がみられることを証明する。
２．インビボでのAgRP細胞選択的刺激によるCRH細胞応答の解析：AgRP Cre::DREADDマウスを用い、CNO投与によりCRHニューロン細胞体が活性化されないことをc-fosの発現により確認する。もし、発現が見られた場合はAgRPニューロンでのc-fosの発現割合を60%食餌制限を10日間行った場合と比較し、AgRPニューロンのうち、食餌制限に反応する割合を明らかにする。さらに、DiIを用いたtracing法によりそれらが正中隆起に投射していることを証明する。
３．AgRP細胞からCRH細胞終末へGABA作動性興奮性投射の生理学的意義の検討：CRH Cre :: NKCC1 floxマウスを用いて、CRHニューロン終末へのGABA入力による興奮を減弱した場合の、CRHニューロン終末での細胞内Ca2+上昇の減弱を確認する。さらに、AgRP Cre :: GAD67 floxマウスないしCRH Cre :: NKCC1 floxマウスを用いて、60%食餌制限ストレスを10日間負荷後のCORT分泌が野生型より低下することを証明する。
４．胎仔における既知HPA軸と新規HPA軸の機能的発達過程の解明： CRH抗体とVGAT抗体を用いて正中隆起へのCRH投射とGABA投射の完成時期を確認し、さらに室傍核CRHニューロンでのKCC2およびNKCC1の発現時期を確認する。

Research Products

• [Int'l Joint Research] Yale School of Medicine(米国)
• [Int'l Joint Research] マインツ大学(ドイツ)
• [Int'l Joint Research] Yale School of Medicine(米国)
• [Int'l Joint Research] マインツ大学(ドイツ)
• [Int'l Joint Research] Yale School of Medicine(アメリカ)
• [Int'l Joint Research] マインツ大学(ドイツ)
• [Journal Article] Chloride homeodynamics underlying modal shifts in cellular and network oscillations (2020)
  • Author(s): Fukuda Atsuo
  • Journal Title: Neuroscience Research Volume: In press
  • DOI: 10.1016/j.neures.2020.02.010
  • Peer Reviewed / Open Access
• [Journal Article] Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. (2019)
  • Author(s): Watanabe M, Zhang J, Mansuri MS, Duan J, Karimy JK, Delpire E, Alper SL, Lifton RP, Fukuda A, Kahle KT.
  • Journal Title: Science Signaling Volume: 12
  • DOI: 10.1126/scisignal.aaw9315
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diverse Actions of Astrocytes in GABAergic Signaling. (2019)
  • Author(s): Masaru Ishibashi, Kiyoshi Egawa, Atsuo Fukuda
  • Journal Title: International Journal of Molecular Sciences Volume: 20(12) Pages: 1-18
  • DOI: 10.3390/ijms20122964
  • Peer Reviewed / Open Access
• [Journal Article] Pathogenic potential of human SLC12A5 variants causing KCC2 dysfunction. (2019)
  • Author(s): Fukuda A and Watanabe M
  • Journal Title: Brain Research Volume: 1710 Pages: 1-7
  • DOI: 10.1016/j.brainres.2018.12.025
  • Peer Reviewed / Open Access
• [Journal Article] Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic Responses in Gad1-Heterozygous Mice Subjected to Prenatal Stress (2018)
  • Author(s): Wang T, Sinha AS, Akita T, Yanagawa Y, Fukuda A
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 12 Pages: 284-284
  • DOI: 10.3389/fncel.2018.00284
  • Peer Reviewed / Open Access
• [Journal Article] MHC class I in dopaminergic neurons suppresses relapse to reward seeking (2018)
  • Author(s): Murakami G, Edamura M, Furukawa T, Kawasaki H, Kosugi I, Fukuda A, Iwashita T, Nakahara D
  • Journal Title: Sci Adv Volume: 4 Pages: 7388-7388
  • DOI: 10.1126/sciadv.aap7388
  • Peer Reviewed / Open Access
• [Journal Article] Optical measurement of glutamate in slice preparations of the mouse retina (2018)
  • Author(s): M. Ohkuma, M. Kaneda, S. Yoshida, A. Fukuda, E. Miyachi
  • Journal Title: Neuroscience Research Volume: 印刷中 Pages: 30544-8
  • DOI: 10.1016/j.neures.2018.03.001
  • Peer Reviewed / Open Access
• [Journal Article] Biallelic Variants in CNPY3. Encoding an Endoplasmic Reticulum Chaperone, Cause Early-Onset Epileptic Encephalopathy. (2018)
  • Author(s): Mutoh, H., M. Kato. T. Akita, T. Shibata, H. Wakamoto, H. Ikeda, H. Kitaura, K. Aoto, M. Nakashima, T. Wang, C. Ohba, S. Miyatake, N. Miyake, A. Kakita, K. Miyake, A. Fukuda, N. Matsumoto, and H. Saitsu.
  • Journal Title: Am J Hum Genet Volume: 102 Issue: 2 Pages: 321-329
  • DOI: 10.1016/j.ajhg.2018.01.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] De novo variants in CAMK2A and CAMK2B cause neurodevelopmental disorders (2018)
  • Author(s): Akita Tenpei、Aoto Kazushi、Kato Mitsuhiro、Shiina Masaaki、Mutoh Hiroki、Nakashima Mitsuko、Kuki Ichiro、Okazaki Shin、Magara Shinichi、Shiihara Takashi、Yokochi Kenji、Aiba Kaori、Tohyama Jun、Ohba Chihiro、Miyatake Satoko、Miyake Noriko、Ogata Kazuhiro、Fukuda Atsuo、Matsumoto Naomichi、Saitsu Hirotomo
  • Journal Title: Annals of Clinical and Translational Neurology Volume: 5 Pages: 280-296
  • DOI: 10.1002/acn3.528
  • Peer Reviewed / Open Access
• [Journal Article] Taurine as an Essential Neuromodulator during Perinatal Cortical Development (2017)
  • Author(s): Kilb W, Fukuda A.
  • Journal Title: Frontiers in Cellular Neuroscience Volume: 11:328 Pages: 328-328
  • DOI: 10.3389/fncel.2017.00328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Two cation current components in GABAergic interneuron precursors in the medial ganglionic eminence of the embryonic brain. (2020)
  • Author(s): Akita T, Fukuda A.
  • Organizer: 第97回日本生理学会大会
• [Presentation] Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. (2020)
  • Author(s): Watanabe M, Kahle KT, Fukuda A.
  • Organizer: 第97回日本生理学会大会
• [Presentation] Orexin receptor activation induces a novel slow afterhyperpolarization that results from the calciumdependentclosure of cation channels in serotonergic dorsal raphe neurons. (2020)
  • Author(s): Ishibashi M, Fukuda A, Leonard CS.
  • Organizer: 第97回日本生理学会大会
• [Presentation] WNK3 kinase maintains basal excitability by regulating inward rectification and intracellular chloride in layer V pyramidal neurons of mouse medial prefrontal cortex. (2020)
  • Author(s): Sinha AS, Wang T, Hosoi Y, Sohara E, Akita T, Uchida S, Fukuda A.
  • Organizer: 第97回日本生理学会大会
• [Presentation] Gad1ヘテロ欠損と胎生期ストレスの二重ヒットはエピジェネティックに統合失調症モデルフェノタイプを誘導する. (2020)
  • Author(s): 福田敦夫.
  • Organizer: 自然科学研究機構分野融合型共同研究事業 ワークショップ「運動・行動から紐解く脳神経回路発達メカニズムの異分野融合研究による解明」
  • Invited
• [Presentation] 発達期のCRHニューロン制御機構におけるGABAの役割. (2020)
  • Author(s): 渡部美穂, 柿沢圭亮, 福田敦夫.
  • Organizer: 自然科学研究機構分野融合型共同研究事業 ワークショップ「運動・行動から紐解く脳神経回路発達メカニズムの異分野融合研究による解明」
• [Presentation] 発達期皮質錐体細胞におけるCa2+動態とタウリンによるGABAA受容体活性化. (2020)
  • Author(s): 石橋賢, 阪東勇輝, 佐藤康二, 福田敦夫.
  • Organizer: 自然科学研究機構分野融合型共同研究事業 ワークショップ「運動・行動から紐解く脳神経回路発達メカニズムの異分野融合研究による解明」
• [Presentation] Gad1 heterozygotes subjected to prenatal stress undergo epigenetic dysregulation of genes perturbing neurodevelopment altering inhibitory network and behavior. (2020)
  • Author(s): Sinha AS, Wang T, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: 自然科学研究機構分野融合型共同研究事業 ワークショップ「運動・行動から紐解く脳神経回路発達メカニズムの異分野融合研究による解明」
• [Presentation] Gad1と出生前ストレスの二重ヒットはエピジェネティックに発達障害を惹起する. (2020)
  • Author(s): 福田敦夫.
  • Organizer: 群馬大学セミナー
  • Invited
• [Presentation] Mutations and posttranslational modulations of the K+-Cl- cotransporter underlie seizures and epilepsy. (2019)
  • Author(s): Fukuda A.
  • Organizer: AuPS/ASB Meeting
  • Int'l Joint Research / Invited
• [Presentation] Astrocytes signaling to control GABA inhibition. (2019)
  • Author(s): Fukuda A.
  • Organizer: Neuroscience/Epilepsy Mini Symposium in UNSW
  • Int'l Joint Research / Invited
• [Presentation] Static magnetic fields decrease excitability of pyramidal neurons by increasing membrane Cl－ conductance in the mouse motor cortex. (2019)
  • Author(s): Sinha AS, Takamatsu Y, Akita T, Mima T, Fukuda A.
  • Organizer: Neural Oscillation Conference 2019
  • Int'l Joint Research
• [Presentation] 背側縫線核セロトニン作動性ニューロンおけるオレキシン誘発性発火後過分極と内向き電流に対する細胞内外カルシウム濃度の影響. (2019)
  • Author(s): 石橋賢, 福田敦夫 , Leonard S Christopher.
  • Organizer: 第46回日本脳科学会
• [Presentation] Static magnetic fields reduce excitability of pyramidal neurons by increasing membrane Cl－ conductance in the mouse motor cortex. (2019)
  • Author(s): Sinha AS、高松泰行, 秋田天平, 美馬達哉, 福田敦夫.
  • Organizer: 第46回日本脳科学会
• [Presentation] Gad1 heterozygotes subjected to prenatal stress undergo epigenetic dysregulation of genes perturbing neurodevelopment and behavioral phenotypes. (2019)
  • Author(s): Wang T, Sinha Adya S, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Excitatory gabaergic inputs to GnRH neurons are required for female reproduction. (2019)
  • Author(s): Watanabe M, Fukuda A.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Impact of a novel slow afterhyperpolarization (sAHP) on spike encoding by serotonergic (5-HT) dorsal raphe (DR) neurons. (2019)
  • Author(s): Ishibashi, M, Berry EA, Molina NE, Sato T, Fukuda A, Leonard CS.
  • Organizer: Neuroscience 2019
  • Int'l Joint Research
• [Presentation] Pivotal roles of Cl-homeostasis in epileptogenesis of human and animal models. (2019)
  • Author(s): Fukuda A.
  • Organizer: 6th Congress of AsCNP
• [Presentation] 胎生期大脳基底核原基の神経前駆細胞に生じる膜電流成分について. (2019)
  • Author(s): 秋田天平, 福田敦夫.
  • Organizer: 第66回中部日本生理学会
• [Presentation] 抑制性神経伝達を維持するカリウム-クロライド共役担体(KCC2)のリン酸化による制御の役割. (2019)
  • Author(s): 渡部美穂, Kahle KT, 福田敦夫.
  • Organizer: 第66回中部日本生理学会
• [Presentation] 背側縫線核セロトニン作動性ニューロンにおけるオレキシン誘発性発火後過分極と内向き電流に対する細胞内外カルシウム濃度の影響. (2019)
  • Author(s): 石橋賢, 福田敦夫 , Leonard S Christopher.
  • Organizer: 第66回中部日本生理学会
• [Presentation] A KCC2 phospho-switch is essential for dynamic GABA-mediated inhibition and postnatal survival. (2019)
  • Author(s): Watanabe M, Zhang J, Mansuri M, Duan J, Kahle KT, Fukuda A.
  • Organizer: 第42回日本神経科学大会
• [Presentation] Static magnetic fields reduce excitability of pyramidal neurons by enhancing membrane Cl- conductance in the mouse motor cortex. (2019)
  • Author(s): Sinha Adya S, Takamatsu Y, Akita T, Mima T, Fukuda A.
  • Organizer: 第42回日本神経科学大会
• [Presentation] Prenatal stress to the Gad1 heterozygotes causes epigenetic changes in neurodevelopment and behavior relating genes and affects their phenotypes. (2019)
  • Author(s): Wang T, Sinha AS, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: 第42回日本神経科学大会
• [Presentation] Effect of orexin on the firing pattern of serotonergic dorsal raphe neurons. (2019)
  • Author(s): Ishibashi M, Fukuda A, Leonard CS.
  • Organizer: 第42回日本神経科学大会
• [Presentation] Prenatal stress to the Gad1 heterozygotes induces neurodevelopmental disorder-like phenotypes along with epigenetic changes in relating genes. (2019)
  • Author(s): Fukuda A
  • Organizer: 2019 International Meeting on Brain Research and Pharmaceutical Science (IMBRP)
  • Int'l Joint Research / Invited
• [Presentation] Cl- homeodynamics and multimodal GABA actions underlying neurological and psychiatric diseases. (2019)
  • Author(s): Fukuda A.
  • Organizer: Guilin medical university special lecture
  • Int'l Joint Research / Invited
• [Presentation] Human epilepsy and animal model with mutations in KCC2. (2019)
  • Author(s): Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Ca2+ signaling and ion channel activation in embryonic neurons in the medial ganglionic eminence. (2019)
  • Author(s): Akita T, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Developmental regulation of KCC2 phosphorylation is essential for GABA signaling and survival. (2019)
  • Author(s): Watanabe M. Zhang J, Mansuri M, Duan J, Kahle KT, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Effect of orexin on the firing pattern of serotonergic dorsal raphe neurons. (2019)
  • Author(s): Ishibashi M, Molina NE, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Prenatal stress on Gad1-heterozygotes perturbs development of GABAergic networks affecting behavior. (2019)
  • Author(s): Wang T, Sinha AS, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Mechanisms underlying WNK3 kinase mediated regulation of neuronal excitability in prefrontal cortex. (2019)
  • Author(s): Sinha AS, Wang T, Hosoi Y, Sohara E, Akita T, Uchida S, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] CRH release regulation by GABAergic projection from arcuate nucleus using chemogenetic model. (2019)
  • Author(s): Yesmin R, Watanabe M, Fukuda A.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Gad1-heterozygotes subjected to prenatal stress undergo alterations in extracellular matrix associated with GABAergic neuron and inhibitory synaptic transmission. (2019)
  • Author(s): Sinha AS, Wang T, Akita T, Yanagawa Y, Fukuda A.
  • Organizer: 第25回浜松医科学シンポジウム
• [Presentation] 細胞内タウリンによるPKC基質部位リン酸化を介したGABAA受容体膜移行維持機構. (2019)
  • Author(s): 細井泰志, 渡部美穂, 秋田天平, 伊藤崇志, 福田敦夫.
  • Organizer: 第5回国際タウリン研究会日本部会
• [Presentation] 胎生期大脳基底核原基の神経前駆細胞内Ca2+シグナリングについて. (2018)
  • Author(s): 秋田天平, 福田敦夫.
  • Organizer: 第65回中部日本生理学会
• [Presentation] GABAによる抑制性伝達におけるカリウム-クロライド共役担体（KCC2）のリン酸化による機能制御の役割. (2018)
  • Author(s): 渡部美穂, Zhang J, Mansuri M, Duan J, Kahle KT, 福田敦夫.
  • Organizer: 第65回中部日本生理学会
• [Presentation] 背側縫線核セロトニン作動性ニューロンにおけるオレキシン誘発性の発火後過分極増強と内向き電流への細胞外カルシウムの影響. (2018)
  • Author(s): 石橋賢, Molina NE, 福田敦夫, Leonard CS.
  • Organizer: 第65回中部日本生理学会
• [Presentation] Alterations of GABAergic Neuron-Associated Extracellular Matrix and Synaptic Responses in Gad1-Heterozygous Mice Subjected to Prenatal Stress. (2018)
  • Author(s): Sinha AS, Wang T, Mutoh H, Akita T, Yanagawa Y, Fukuda A.
  • Organizer: 第65回中部日本生理学会
• [Presentation] Development of chemogenetic model to study physiological roles of the GABAergic projection from arcuate nucleus to the CRH nerve terminals. (2018)
  • Author(s): Yesmin R, Watanabe M, Fukuda A.
  • Organizer: 第65回中部日本生理学会
• [Presentation] Effect of orexin on the firing pattern of serotonergic dorsal raphe neurons. (2018)
  • Author(s): Ishibashi M, Molina NE, Fukuda A, Leonard CS.
  • Organizer: 第45回日本脳科学会
• [Presentation] てんかんにおけるGABAシナプスの役割. (2018)
  • Author(s): 福田敦夫.
  • Organizer: 第61回日本脳循環代謝学会学術集会
  • Invited
• [Presentation] Prenatal stress to the GAD67 heterozygous mice impairs GABA neurogenesis followed by physiological dysfunctions in postnatal life. (2018)
  • Author(s): Fukuda A.
  • Organizer: 第40回日本生物学的精神医学会・第61回日本神経化学会大会 合同年会
  • Invited
• [Presentation] Prenatal stress on Gad1-heterozygotes selectively perturbs GABAergic neurogenesis, GABAergic synapse function and behavioral phenotypes. (2018)
  • Author(s): Wang T, Sinha AS, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: 第7回日本DOHaD学会
• [Presentation] Cl-ホメオダイナミクスとマルチモーダルGABA:脳での多彩な働き. (2018)
  • Author(s): 福田敦夫.
  • Organizer: 第65回脳の医学・生物学研究会
  • Invited
• [Presentation] WNK3 Kinase regulates inwardly rectifying potassium channels in layer V pyramidal neurons of the mouse prefrontal cortex. (2018)
  • Author(s): Sinha AS, Hosoi Y, Sohara E, Mutoh H, Akita T, Uchida S, Fukuda A.
  • Organizer: 第41回日本神経科学大会
• [Presentation] Prenatal stress on Gad1-heterozygotes selectively perturbs GABAergic neurogenesis, GABAergic synapse function and behavioral phenotypes. (2018)
  • Author(s): Wang T, Sinha AS, Mutoh H, Akita T, Yanagawa Y, Kawai T, Hata K, Fukuda A.
  • Organizer: 第41回日本神経科学大会
• [Presentation] De novo mutants of CaMKIIα/β responsible for neurodevelopmental disorders upregulate A-type voltage-dependent K+ currents in hippocampal neurons. (2018)
  • Author(s): Akita T, Aoto K, Kato M, Shiina M, Mutoh H, Nakashima M, Kuki I, Okazaki S, Magara S, Shiihara T, Yokochi K, Aiba K, Tohyama J, Ohba C, Miyatake S, Miyake N, Ogata K, Fukuda A, Matsumoto N, Saitsu H.
  • Organizer: 第41回日本神経科学大会
• [Presentation] Regulated Phosphorylation of KCC2 at Thr906/Thr1007 is essential for activity-dependent Cl-extrusion during normal brain development. (2018)
  • Author(s): Fukuda, A.
  • Organizer: FENS forum 2018
  • Int'l Joint Research
• [Presentation] 神経・精神疾患の病因・病態仮説としてのマルチモーダル GABA. (2018)
  • Author(s): 福田敦夫.
  • Organizer: お茶の水ニューロサイエンスセミナー
  • Invited
• [Presentation] Maternal taurine modulate fetal brain development via intracellular and extracellular effectors. (2018)
  • Author(s): Fukuda, A.
  • Organizer: The 21st International Taurine Meeting
  • Int'l Joint Research
• [Presentation] Diverse Actions of Astrocytes at GABAergic Tripartite Synapses in Seizures: Are they protective or exacerbative? (2018)
  • Author(s): Fukuda, A.
  • Organizer: 2018 Symposium on Functional Interactions among Glia and Neurons
  • Int'l Joint Research / Invited
• [Presentation] De novo CaMKⅡα/β mutants causing neurodevelopmental disorders upregulate A-type voltage-dependent K+ currents in hippocampal neurons. (2018)
  • Author(s): Akita T, Aoto K, Fukuda A, Matsumoto N, Saitsu H.
  • Organizer: 第95回日本生理学会大会
• [Presentation] WNK3 kinase regulates inwardly rectifying potassium current in layer V pyramidal neurons of the mouse prefrontal cortex. (2018)
  • Author(s): Sinha Adya S, Hosoi Y, Sohara E, Mutoh H, Akita T, Uchida S, Fukuda A.
  • Organizer: 第95回日本生理学会大会
• [Presentation] Temporally genetic expression of KCC2 in GnRH neurons in vivo causes impairment of fertility. (2018)
  • Author(s): Watanabe M, Nabekura J, Fukuda A.
  • Organizer: 第95回日本生理学会大会
• [Presentation] タウリン欠乏はGABAA受容体のリン酸化状態を変化させることにより大脳皮質感覚野錐体細胞におけるポストシナプスのGABAA受容体数を減少させる. (2018)
  • Author(s): 細井泰志, 渡部美穂, 秋田天平, 武藤弘樹, 伊藤崇志, 福田敦夫.
  • Organizer: 第4回国際タウリン研究会日本部会
• [Presentation] The role of GABAergic interneuron-astrocyte interaction in epileptic seizures. (2018)
  • Author(s): Mutoh, H., Fukuda, A.
  • Organizer: 第１回山梨大学先端脳科学特別教育プログラム国際シンポジウム
  • Int'l Joint Research
• [Presentation] GABA synaptic dynamics and astrocytic Cl- buffering underlying neural network oscillation. (2017)
  • Author(s): 福田敦夫.
  • Organizer: 第47回日本臨床神経生理学会学術大会
• [Presentation] A novel CRH secretory mechanism by an excitatory GABAergic input from the arcuate nucleus to the median eminence. (2017)
  • Author(s): Fukuda, A.
  • Organizer: The 17th Hamamatsu-Kyungpook Joint Medical Symposium
  • Int'l Joint Research / Invited
• [Presentation] Regulation of inwardly rectifying potassium current by WNK3 kinase in layer V pyramidal neurons of the mouse prefrontal cortex. (2017)
  • Author(s): Sinha Adya, S., Hosoi, Y., Sohara, E., Mutoh, H., Akita, T., Uchida, S., Fukuda, A.
  • Organizer: The 17th Hamamatsu-Kyungpook Joint Medical Symposium
  • Int'l Joint Research
• [Presentation] Prenatal stress on Gad1-heterozygotes perturbs GABAergic neurogenesis, GABAergic synapse formation and behavioral phenotypes. (2017)
  • Author(s): Fukuda, A. Wang, T., Sinha Adya, S., Yanagawa, Y., Kawai, T. and Hata, K.
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Constitutive phosphomimetic inhibition of KCC2 at Thr906/Thr1007 causes GABA-dependent network excitability, seizure, and early postnatal death. (2017)
  • Author(s): Watanabe, M., Duan, J., Mansuri, M., Zhang, J., Fukuda, A. and Kahle, K.T.
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Presentation] KCC2 dysfunction underlying infantile and neonatal seizures in an animal model. (2017)
  • Author(s): 福田敦夫, 渡部美穂, 秋田天平, Kahle, K.
  • Organizer: 第51回日本てんかん学会学術集会
• [Presentation] Prenatal stress on Gad1- heterozygotes affects inhibitory synaptic transmission. (2017)
  • Author(s): Wang, T., Sinha Adya, S., Akita, T., Yanagawa, Y., Fukuda, A.
  • Organizer: 生理学研究所研究会「シナプス・神経回路機能の時空間制御」
• [Presentation] Prenatal stress on Gad1-heterozygotes perturbs development of brain and behavior by epigenetic mechanism. (2017)
  • Author(s): Wang T, Sinha AS, Yanagawa Y, Kawai T, Hata K and Fukuda A.
  • Organizer: 第44回日本脳科学会
• [Presentation] Regulation of inwardly rectifying potassium current by WNK3 kinase in layer V pyramidal neurons of the mouse prefrontal cortex. (2017)
  • Author(s): Sinha Adya, S., Hosoi, Y., Sohara, E., Mutoh, H., Akita, T., Uchida, S. and Fukuda, A.
  • Organizer: 第64回中部日本生理学会
• [Presentation] 生殖腺刺激ホルモン放出ホルモン(GnRH)ニューロン制御における興奮性GABA入力の役割. (2017)
  • Author(s): 渡部美穂, 鍋倉淳一, 福田敦夫.
  • Organizer: 第64回中部日本生理学会
• [Presentation] てんかん原性獲得過程における抑制性神経とグリア細胞の相互作用. (2017)
  • Author(s): 武藤弘樹, 福田敦夫.
  • Organizer: 第64回中部日本生理学会
• [Presentation] A novel CRH secretory mechanism by GABAergic input from the arcuate nucleus to the axon terminals of high [Cl-]i. (2017)
  • Author(s): Fukuda, A.
  • Organizer: Seminar of Center for Neuron-Glia Interaction, KIST(Korea Institute of Science and Technology)
  • Int'l Joint Research / Invited
• [Presentation] Taurine depletion reduces postsynaptic GABAA receptors in layer 2/3 pyramidal neurons of the somatosensory cortex. (2017)
  • Author(s): Hosoi, Y., Akita, T., Watanabe, M., Mutoh, H., Miyajima, H. and Fukuda, A.
  • Organizer: XXIII World Congress of Neurology（WCN2017）
  • Int'l Joint Research
• [Presentation] 母体ストレスとGABAが仔脳発達に与える病態生理学的影響. (2017)
  • Author(s): 福田敦夫, 王天英, Sinha Adya S, 柳川右千夫, 河合智子, 秦健一郎.
  • Organizer: 第27回日本病態生理学会大会
• [Presentation] Regulation of inwardly rectifying potassium current by WNK3 kinase in layer V pyramidal neurons of the mouse prefrontal cortex. (2017)
  • Author(s): Sinha Adya, S., Hosoi,Y., Sohara, E., Mutoh, H., Akita, T., Uchida, S. and Fukuda, A.
  • Organizer: 第40回日本神経科学大会
• [Presentation] The role of GABAergic interneuron-astrocyte interaction in epileptic seizures. (2017)
  • Author(s): Mutoh, H., Fukuda, A.
  • Organizer: 第40回日本神経科学大会
• [Presentation] Cellular Mechanisms Underlying Status Epilepticus: what do animal models tell us? (2017)
  • Author(s): Fukuda, A.
  • Organizer: The 19th Annual Meeting of Infantile Seizure Society International Symposium on Status Epilepticus in Infants and Children
  • Int'l Joint Research / Invited
• [Presentation] Prenatal stress on Gad1-heterozygotes selectively perturbs parvalbumin (PV)-positive GABAergic neurogenesis, GABA synapses and social interaction behavior. (2017)
  • Author(s): Wang, T., Sinha Adya, S., Yanagawa, Y., Kawai, T., Hata, K. and Fukuda, A.
  • Organizer: IBNS 26th Annual Meeting
  • Int'l Joint Research
• [Remarks] 浜松医科大学医学部神経生理学講座ホームページ
  • URL: https://www.hama-med.ac.jp/education/fac-med/dept/neurophysiology/index.html
• [Remarks] 浜松医科大学プレスリリース「米国科学振興協会の科学雑誌に研究成果が公表されました」
  • URL: https://www.hama-med.ac.jp/topics/2019/25433.html
• [Remarks] 日本生理学会ホームページ サイエンストピックス
  • URL: http://physiology.jp/science-topic/22726/
• [Remarks] 浜松医科大学医学部神経生理学講座ホームページ
  • URL: http://www.hama-med.ac.jp/uni_education_igakubu_igaku_seiri1.html