The pharmacological properties of tonic currents mediated by GABAA-Rs in BLA neurons

• Project/Area Number: 23590276
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology (including Physical medicine and Nutritional physiology)
• Research Institution: Hirosaki University
• Principal Investigator: YAMADA JUNKO 弘前大学, 医学(系)研究科(研究院), 講師 (30334965)
• Co-Investigator(Kenkyū-buntansha): 冨山 誠彦 弘前大学, 医学(系)研究科(研究院), 研究員 (40311542)
• Co-Investigator(Renkei-kenkyūsha): UENO Shinya 弘前大学, 大学院医学研究科, 教授 (00312158) ; MIGITA Keisuke 弘前大学, 大学院医学研究科, 助教 (10352262)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: GABA / 抑制 / トニック抑制 / 不安 / 性差 / GABAA受容体 / Tonic / Synapse

Research Abstract

Synaptically released GABA acting on postsynaptic GABAA receptor produce not only phasic inhibition, but also tonic inhibition by persistent activation of extrasynaptic receptors. This study aimed at examining pharmacological properties of tonic currents mediated by GABAA-Rs in BLA neurons of sex differences using the wild type and PRIP-1 KO mice which is known of downregulation of GABAergic transmission. The application of GABAA-R antagonist bicuculline blocked tonic GABAergic current which was significantly larger than those in KO. Bath application of diazepam and zolpidem causes increase tonic conductance in WT. In contrast, PRIP-1 KO mice showed lower sensitivity to these compounds. These data indicate that tonic GABAergic inhibition exist in principal neurons of the basolateral amygdala in WT mice but PRIP-1 KO mice have imperfection of this inhibitory system.

Research Products

• [Journal Article] Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motorcortex of a rat model of levodopa-induced dyskinesia. (2014)
  • Author(s): Ueno T, Yamada J, Nishijima H, Arai A, Migita K, Baba M, Ueno s, Tomiyama M.
  • Journal Title: Neurobiology of Disease Volume: 64 Pages: 142-9
  • DOI: 10.1016/j.nbd.2013.12.014
  • Peer Reviewed / Open Access
• [Journal Article] Morphologic changes of dendritic spines of striatal neurons in the levodopa-induced dyskinesia model (2014)
  • Author(s): Nishijima H, Suzuki S, Kon T, Funamizu Y, Ueno T, Haga R, Suzuki C, Arai A, Kimura T, Suzuki C, Meguro R, Miki Y, Yamada J, Migita K, Ichinohe N, Ueno S, Baba M, Tomiyama M
  • Journal Title: Mov Disord Volume: 29 Suppl 3 Issue: 3 Pages: 336-343
  • DOI: 10.1002/mds.25826
  • Peer Reviewed
• [Journal Article] A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) (2013)
  • Author(s): Yamada J., Zhu G., Okada M., Hirose S., Yoshida S., Shiba Y., Migita K., Mori F., Sugawara T., Chen L., LiuF., Yoshida S., Ueno S., Kaneko S
  • Journal Title: Epi. Res Volume: 107(1-2) Pages: 127-137
  • Peer Reviewed
• [Journal Article] Cl^- homeodynamics in gap-junction-coupled astrocytic networks on activation of GABAergic synapses (2013)
  • Author(s): Egawa K., Yamada J., Furukawa T., Yanagawa Y., Fukuda A
  • Journal Title: J. Physiol Volume: 591 Pages: 3901-3917
  • Peer Reviewed
• [Journal Article] Properties of a Novel GABA(A) Receptorγ(2) Subunit Mutation Associated With Seizures (2013)
  • Author(s): Migita K, Yamada J, Nikaido Y, Shi X, Kaneko S, Hirose S, Ueno S
  • Journal Title: J. Pharmacol. Sci Volume: 121(1) Pages: 84-87
  • Peer Reviewed
• [Journal Article] Drebrin immunoreactivity in the striatum of a rat model of levodopa-induced dyskinesia. (2013)
  • Author(s): Nishijima H, Arai A, Kimura T, Mori F, Yamada J, Migita K, Wakabayashi K, Baba M, Ueno S, Tomiyama M.
  • Journal Title: Neuropathology Volume: 33 Issue: 4 Pages: 391-6
  • DOI: 10.1111/neup.12009
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=23241013
  • Peer Reviewed
• [Journal Article] Cl- homeodynamics in gap-junction-coupled astrocytic networks on activation of GABAergic synapses. (2013)
  • Author(s): Egawa K., Yamada J., Furukawa T., Yanagawa Y., Fukuda A
  • Journal Title: The Journal of physiology Volume: 591 Issue: 16 Pages: 3901-3917
  • DOI: 10.1113/jphysiol.2013.257162
  • Peer Reviewed
• [Journal Article] A novel prophylactic effect of furosemide treatment on autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). (2013)
  • Author(s): Yamada J, Zhu G, Okada M, Hirose S,
  • Journal Title: Epilepsy Res. Volume: 107 Issue: 1-2 Pages: 127-137
  • DOI: 10.1016/j.eplepsyres.2013.08.018
  • Peer Reviewed
• [Journal Article] Properties of a Novel GABA(A) Receptor γ(2) Subunit Mutation Associated With Seizures. (2013)
  • Author(s): Migita K, Yamada J, Nikaido Y, Shi X, Kaneko S, Hirose S, Ueno S.
  • Journal Title: Journal of Pharmacological Sciences Volume: 121(1): Pages: 84-7
  • Peer Reviewed
• [Journal Article] Taurine inhibits K^+-Cl^- cotransporter KCC2 to regulate embryonic Cl^- homeostasis via with-no-lysine (WNK) protein kinase signaling pathway (2012)
  • Author(s): Inoue K, Furukawa T, Kumada T, Yamada J, Wang T, Inoue R, Fukuda A
  • Journal Title: J Biol Chem Volume: 287 Issue: 25 Pages: 20839-20850
  • DOI: 10.1074/jbc.m111.319418
  • Peer Reviewed
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in PRIP-1 KO mice is associated with an epilepsy phenotype (2011)
  • Author(s): Zhu G., Yoshida S., Migita K., Yamada J., Ueno S
  • Journal Title: J Pharmacol Exp Ther Volume: 340(3) Issue: 3 Pages: 520-8
  • DOI: 10.1124/jpet.111.182386
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22128345
  • Peer Reviewed
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice (2011)
  • Author(s): Migita K., Tomiyama M., Yamada J., Fukuzawa M., Kanematsu T., Hirata M., Ueno S
  • Journal Title: Molecular pain Volume: 7 Pages: 79-79
  • DOI: 10.1186/1744-8069-7-79
  • URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22008183
  • Peer Reviewed
• [Journal Article] 痛み (2011)
  • Author(s): 右田啓介, 山田順子, 上野伸哉
  • Journal Title: 月刊臨床神経科学(中外医学社) Volume: 29 Pages: 836-838
• [Journal Article] Phenotypes of pain behavior in phospholipase C-related but catalytically inactive protein type 1 knockout mice. (2011)
  • Author(s): Migita K., Tomiyama M., Yamada J., Fukuzawa M., Kanematsu T., Hirata M., Ueno S
  • Journal Title: Molecular pain Volume: 7 Pages: 79-79
  • Peer Reviewed
• [Journal Article] Dysfunction of extrasynaptic GABAergic transmission in PRIP-1 KO mice is associated with an epilepsy phenotype. (2011)
  • Author(s): 1.Zhu G., Yoshida S., Migita K., Yamada J., Mori F., Tomiyama M., Wakabayashi K., Kanematsu T., Hirata M., Kaneko S., Ueno S and Okada M.
  • Journal Title: J Pharmacol Exp Ther. Volume: 340 (3): Pages: 520-8
  • Peer Reviewed
• [Presentation] "古くて新しいGABAの機能"The role of GABAergic tonic signal in the pathophysiology (2013)
  • Author(s): 山田順子
  • Organizer: 第36回日本神経科学会Neuro2013シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] "抑制性伝達とそれを担う機能分子のダイナミクス"(オーガナイザー)"Role of GABAA receptor mediated tonic conductance in physiology and pathology (2013)
  • Author(s): 山田順子
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-27
• [Presentation] Role of GABAA receptor mediated tonic conductance in phsyiology and pathology (2013)
  • Author(s): Junko Yamada
  • Organizer: 第90回日本生理学会大会 シンポジウム
  • Place of Presentation: 東京
• [Presentation] Dysfunction of tonic GABAergic transmission in PRIP-1 KO mice (2012)
  • Author(s): Junko Yamada
  • Organizer: The 10th Korea-Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscle Sciences Gyeongju, Korea
  • Place of Presentation: Korea
  • Year and Date: 2012-02-17
• [Presentation] Spontaneous epileptic seizures in a missense mutation V286L (CHRNB2) transgenic rat harboring human autosomal-dominant nocturnal frontal lobe epileps (2012)
  • Author(s): Shiba Y., Yamada J., Migita K., Mori F., Wakabayashi K., Kaneko S., Okada M., Hirose S. & Ueno S.
  • Organizer: FENS 2012
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] Down-regulation of tonic GABAergic transmission upon PRIP-1 disruption in basolateral amygdala (2012)
  • Author(s): Yamada J., Migita K., Shiba Y., Kanematsu T., Hirata M. & Ueno S.
  • Organizer: FENS 2012
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] Delayed induction of anesthesia by propofol in mice deficient in phospholipase C-related but catalytically inactive protein type-1 (2012)
  • Author(s): Nikaido Y., Yamada J., Migita K., Shiba Y., Kushikata T., Hirota K., Kanematsu T., Hirata M. & Ueno S.
  • Organizer: FENS 2012
  • Place of Presentation: バルセロナ（スペイン）
• [Presentation] GABAA receptor via phospholipase C-related but catalytically inactive protein type 1 in the spinal cord participate in abnormal pain sensation (2012)
  • Author(s): Keisuke Migita1, Masahiko Tomiyama1, Junko Yamada1, Yoshikazu Nikaido1, Takashi Kanematsu2, Masato Hirata3 and Shinya Ueno1
  • Organizer: SFN 2012
  • Place of Presentation: ニューオリンズ（北米）
• [Presentation] Phospholipase C-related, but catalytically inactive protein-1（PRIP-1）欠損マウスの表現型解析 (2012)
  • Author(s): 上野 伸哉、山田 順子、右田 啓介 兼松 隆 平田 雅人
  • Organizer: 第39回日本脳科学学会
  • Place of Presentation: 小倉
• [Presentation] Dysfunction of tonic GABAergic transmission in PRIP-1 KO mice (2012)
  • Author(s): Junko Yamada, Keisuke Migita, Yuko Shiba, Takashi Kanemnatsu, Masato Hirata, Shinya Ueno
  • Organizer: The 10th Korea-Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscle Sciences(招待講演)
  • Place of Presentation: Gyeongju, Republic of Korea
• [Presentation] てんかん患者由来GABAA受容体2サブユニット(N40S)変異受容体の薬理学的特性 (2012)
  • Author(s): Keisuke Migitaa, Junko Yamadaa, XiuYu Shic, Sunao Kaneko, Shinichi Hirosec, Shinya Ueno
  • Organizer: 第85回薬理学会年会
  • Place of Presentation: 横浜
• [Presentation] Involvement of the subregions of medial prefrontal cortex in processing of the affective odors, green odor and predator odor, in the freely moving rat (2012)
  • Author(s): Nikaido, Yoshikazu; Yamada, Junko; Migita, Keisuke; Shiba, Yuko; Ueno, Shinya
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
• [Presentation] PRIP-1 KOマウスにおける麻酔導入の遅延 (2012)
  • Author(s): 二階堂 義和、山田 順子、右田 啓介、柴 祐子、兼松 隆、平田 雅人、上野 伸哉
  • Organizer: ニューロサイエンス研究会
  • Place of Presentation: 弘前
• [Presentation] Interaction of nervous and immune systems in health and disease (2011)
  • Author(s): Junko Yamada
  • Organizer: IIIInternational symposium
  • Place of Presentation: Saint Petersburg, Russia
  • Year and Date: 2011-06-04
• [Presentation] TONIC GABAERGIC TRANMISSION IN BLA NEURONS (2011)
  • Author(s): Yamada,J., Migita K., Shiba Y., Kanemnatsu T., Hirata M., Ueno S.
  • Organizer: III International symposium "Interaction of nervous and immune systems in health and disease"(招待講演)
  • Place of Presentation: Saint Petersburg, Russia
• [Presentation] Phenotype analysis of transgenic rat harboring a missense mutation V286L of Chrnb2 identified in autosomal dominant nocturnal frontal lobe epilepsy (2011)
  • Author(s): 柴 祐子, 山田 順子, 右田 啓介, 森 文秋, 若林 孝一, 兼子 直, 岡田 元宏, 廣瀬 伸一,上野 伸哉
  • Organizer: Neuroscience 2011
  • Place of Presentation: 横浜
• [Presentation] Morphologic changes of spines in the striatum of a rat model of L-DOPA-induced dyskinesias (2011)
  • Author(s): Nishijima H., Tomiyama M., Arai A., Meguro R., Yamada J., Migita K., Ichinohe N., Shinya U.
  • Organizer: Neuroscience 2011
  • Place of Presentation: 横浜
• [Presentation] Developmental regulationof KCC2 activity by taurine in a phosphorylation-dependent manner (2011)
  • Author(s): Inoue K., Furkukawa T., Yamada J., Kumada T., Wang T., Inoue R., Fukuda A.
  • Organizer: Neuroscience 2011
  • Place of Presentation: 横浜