中枢グルタミン酸受容体の分子構造と生理機能

• Project/Area Number: 04267103
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Research Institution: The University of Tokyo (1994); Niigata University (1992-1993)
• Principal Investigator: 三品 昌美 東京大学, 医学部(医), 教授 (80144351)
• Co-Investigator(Kenkyū-buntansha): 遠山 正彌 大阪大学, 医学部, 教授 (40028593) ; 杉山 博之 九州大学, 理学部, 教授 (20124224) ; 津本 忠治 大阪大学, 医学部, 教授 (50028619) ; 小澤 瀞司 群馬大学, 医学部, 教授 (40049044) ; 川合 述史 自治医科大学, 教授 (00073065) ; 渡辺 雅彦 北海道大学, 医学部, 助教授 (70210945) ; 相沢 慎一 新潟大学, 理化学研究所, 副主任研究員 (60073011) ; 勝木 元也 九州大学, 生体防御医学研究所, 教授 (20051732)
• Project Period (FY): 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥194,000,000 (Direct Cost: ¥194,000,000); Fiscal Year 1994: ¥54,000,000 (Direct Cost: ¥54,000,000); Fiscal Year 1993: ¥72,500,000 (Direct Cost: ¥72,500,000); Fiscal Year 1992: ¥67,500,000 (Direct Cost: ¥67,500,000)
• Keywords: グルタミン酸受容体 / NMDA受容体チャネル / 脳 / 長期増強 / スライス / 標的遺伝子組換え / パッチクランプ / 海馬 / G蛋白共役型グルタミン酸受容体 / カルシウム / 脱感作 / 標的組換え / mRNA

Research Abstract

本研究班は、中枢における神経情報伝達シナプス可塑性の鍵を握るグルタミン酸受容体を実体として明らかにするとともにその生理機能を分子構造と対応させて明確にすることを目標とした。研究計画が順調に進行していることから、本年度は生理機能を分子レベルで理解することに重点をおいて、以下の成果を挙げた。NMDA受容体チャネルのε1サブユニット遺伝子を不活化されたマウスを作成し、海馬シナプスにおける長期増強と空間学習の低下が起こることを見い出した。この成果は、記憶・学習のシナプス可塑性仮説を支持するものである(三品)。短時間虚血負荷後のスナネズミ海馬錘体細胞においてAMPA型グルタミン酸受容体チャネル電流の持続性やカルシウム透過性が変化することを単一チャネル電流の解析により明らかにした(川合)。海馬切片を対象として、スライスパッチクランプ法とRT-PCR法を組み合わせることにより、グルタミン酸受容体チャネルの電気生理学的特性とサブユニット構成との関連を明らかにした(小澤)。ラット視覚野から調整した培養神経細胞標本に穿孔パッチクランプ法を適用することにより、視覚野におけるシナプス長期増強の誘発にはシナプス後細胞の脱分極と同期したシナプス前部の賦括が必要であることを見い出した(津本)。代謝型グルタミン酸受容体のサブタイプ5にはスプライシングの違いによる2種類の型が存在し、発生の時期により調節されていることを見い出した(杉山)。AMPA型グルタミン酸名受容体チャネルmRNAがラットの腺細胞に発現していることならびに虚血条件下ではグルタミン酸トランスポーターの遺伝子発現と蛋白の細胞内局在が変化することを見い出した(遠山)。ホメオ蛋白Otx2遺伝子のヘテロ欠損マウスを作製し、Otx2が頭蓋においても神経系においても下顎セグメントの形態形成を特異的に制御することを明らかにした(相沢)。5種類のNMDA受容体チャネルサブユニットの遺伝子発現パターンは生後2週間の間に、領域差の小さい胎児型から顕著な空間的異質性を特徴とする成熟型へと変換することを明らかにした(渡辺)。バキュロウイルス発現系により大量発現させたAMPA型およびNMDA型グルタミン酸受容体チャネルを用いて、リガンド結合活性にN-グリコシル化が必須であることを明らかにした(川本)。

Research Products

• [Publications] Watanabe,M.: "Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina." Brain Res.634. 328-332 (1994)
• [Publications] Watanabe,M.: "Distinct gene expression of the N-methyl-D-aspartate receptor channel subunit in peripheral neurons of the mouse sensory ganglia and adrenal gland." Neurosci. Lett.165. 183-186 (1994)
• [Publications] Ishida,N.: "Circadian expression of NMDA receptor mRNAs, ε3 and ζ1, in the suprachiasmatic nucleus of rat brain." Neurosci. Lett.166. 211-215 (1994)
• [Publications] Watanabe,M.: "Distinct spatio-temporal expressions of five NMDA receptor channel subunit mRNAs in the cerebellum." J. Comp. Neurol.343. 513-519 (1994)
• [Publications] Watanabe,M.: "Distinct distributions of five NMDA receptor channel subunit mRNAs in the brainstem." J. Comp. Neurol.343. 520-531 (1994)
• [Publications] Watanabe,M.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the mouse cervical cord." J. Comp. Neurol.345. 314-320 (1994)
• [Publications] Nakano,R.: "A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis." Biochem. Biophys. Res. Commun.200. 695-703 (1994)
• [Publications] Kawamoto,S.: "Ligand binding properties and N-glycosylation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selective glutamate receptor channel expressed in a Baculovirus system." Eur. J. Biochem.223. 665-673 (1994)
• [Publications] Takahasi,H.: "Familial amyotrophic lateral sclerosis with a mutation in the Cu/Zn superoxide dismutase gene." Acta Neuropathol.88. 185-188 (1994)
• [Publications] Tsuzuki,K.: "Ion permeation properties of the cloned mouse ε2/ζ1 NMDA receptor channel." Mol. Brain Res.26. 37-46 (1994)
• [Publications] Hattori,S.: "Expression and characterization of the α2 subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selective glutamate receptor channel in a Baculovirus system." Brain Res.666. 43-52 (1994)
• [Publications] Mori,H.: "Different spatio-temporal expressions of three otx homeoprotein transcripts during zebrafich embryogenesis." Mol. Brain Res.27. 221-231 (1994)
• [Publications] Hirano,T.: "Involvement of the glutamate receptor δ2 subunit in the long-term depression of glutamete responsiveness in cultured Purkinje cells." Neurosci. Lett.182. 172-176 (1994)
• [Publications] Sakimura,K.: "Reduced hippocampal LTP and spatial learning of mice lacking NMDA receptor ε1 subunit." Nature. 373. 151-155 (1995)
• [Publications] Hirano,T.: "Suppression of LTD in cultured Purkinji cells deficient of glutamate receptor δ2 subunit." NeuroReport. (印刷中). (1995)
• [Publications] Kawamoto,S.: "N-linked glycosylation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate(AMPA)-selective glutamate receptor channel α2 subunit is essential for the acquisition of ligand-binding activity." J.Neurochem.(印刷中). (1995)
• [Publications] Kawamoto,S.: "Expression and characterization of the ζ1 subunit of the N-methyl-D-aspartate(NMDA) receptor channel in a Baculovirus system." Mol. Brain Res.(印刷中). (1995)
• [Publications] Iino,M.: "Relationship between calcium permeability and rectification properties of AMPA receptors in cultured rat hippocampal neurons." Neurosci. Lett.173. 14-16 (1994)
• [Publications] Tsuzuki,K.: "Ion permeation properties of the cloned mouse ε2/ζ1 NMDA receptor channel." Mol. Brain Res.26. 37-46 (1994)
• [Publications] Inoue,T.: "Experimental model for MDS-like myelodysplasia in transgenic mice harboring the SV40 large-T antigen under an immunoglobulin enhancer." Leukemia(Suppliment). 8. 202-205 (1994)
• [Publications] Hashimoto,N.: "Parthenogenetic activation of oocytes in c-mos-deficient mice." Nature. 370. 68-71 (1994)
• [Publications] Yagi,T.: "Fyn expression during early neurogenesis in mouse embryos." Oncogene. 9. 2433-2440 (1994)
• [Publications] Tamemoto,H.: "Inslin resistance and growth retardation in mice lacking inslin receptor substrate-1." Nature. 372. 182-185 (1994)
• [Publications] Aizawa,S.: "Non-receptor tyrosine kinases in mammalian neurogenesis." Proceedings of the Princess Takamatsu Symposium. 24. 323-337 (1994)
• [Publications] Yoshida,M.: "A new strategy of gene-trapping in ES cells using 3'-RACE." Transgenic Research. 4(印刷中). (1995)
• [Publications] Nakamura,K.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamate receptors in frog oocytes." J. Physiol. (Lond.). 474. 35-41 (1994)
• [Publications] Sugiyama,H.: "Molecular and functional properties of metabotropic glutamate receptors in the brain." Biomed Res.15. 29-31 (1994)
• [Publications] Minakami,R.: "Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype 5." Biochem. Biophys. Res. Commun.199. 1136-1143 (1994)
• [Publications] Kasahara,J.: "Inositol phospholipid metabolism in Xenopus oocytes mediated by endogenous Go and Gi proteins." FEBS Lett.355. 41-44 (1994)
• [Publications] Tsubokawa,H.: "Inositol 1,3,4,5-tetrakisphosphate(IP_4) as a mediator of neuronal death in ischemic hippocampus." Neurosi.59. 291-297 (1994)
• [Publications] Shimazaki,K.: "Changes in inositol 1,4,5-triphosphate 3-kinase immunoreactivity following transient ischemia in gerbil hippocampus." NeuroReport. 5. 785-788 (1994)
• [Publications] Tsubokawa,H.: "Ca^<2+>-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons." J. Neurophysiol.71. 1190-1196 (1994)
• [Publications] Shimazaki,K.: "Increase in bc1-2 oncoprotein and the tolerance to ischemia-induced neuronal death in the gerbli hippocampus." Neurosci. Res.20. 95-99 (1994)
• [Publications] Ishida,A.: "An electrophysiological and immunohistochemical study of the hippocampus of the reelermutant mouse." Brian Res.662. 60-68 (1994)
• [Publications] Yoshimura,Y.: "Dependance of LTP induction on postsynaptic depolarization: A proforated patch clamp study in visual cortical slices of young rats." J. Neurophysiol.71. 1638-1645 (1994)
• [Publications] Funauchi,M.: "Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase calcineurin, on induction of long-term potentiation in rat visual cortex." Neurosci. Res.19. 269-278 (1994)
• [Publications] Sato,H.: "Broad-tuned chromatic inputs to color-selective neurons in the monkey visual cortex." J. Neurophysiol.72. 163-168 (1994)
• [Publications] Lin,M.-H.: "Intracellular calcium increase induced by GABA in visual cortex of fetal and neonatal rats and its disappearance with development." Neurosci. Res.20. 85-94 (1994)
• [Publications] Haruta,H.: "Induction of LTD but not LTP through metabotropic glutamate receptors in visual cortex." NeuroReport. 5. 1829-1832 (1994)
• [Publications] Takahashi,Y.: "NMDA receptors contribute to afferent synaptic transmission in the medial vestibular nucleus of young rats." Brain Res.659. 287-291 (1994)
• [Publications] Takahashi,Y.: "NMDA receptor-mediated increase of intraneuronal Ca^<2+> in the medial vestibular nucleus of young rats." Neurosci. Res.21. 59-70 (1994)
• [Publications] Torii,N.: "An inhibitor for calcium, FK506, blocks induction of long-term depression in rat visual cortex." Neurosci. Lett.184(印刷中). (1994)
• [Publications] Kamishita,T.: "Metabotropic glutamate receptors and visual cortical synaptic plasticity." Canadian J. Physiol. Pharmacol.73(印刷中). (1995)
• [Publications] Watanabe,M.: "Molecular cloning of rat cDNAs for ζ and θ subtypes of 14-3-3 protein and differential distributions of their mRNAs in the brain." Mol. Brain Res.25. 113-121 (1994)
• [Publications] Watanabe,M.: "Differential expressions of the topoisomerase IIα and IIβ mRNAs in developing rat brain." Neurosci. Res.19. 51-57 (1994)
• [Publications] Fujita,S.: "Expression of NMDA receptor subunit mRNA in the vestibular ganglion of the rat and guinea-pig." NeuroReport. 5. 862-864 (1994)
• [Publications] Tohyama,M.: "Gene expression of neuroreceptors in the locus coeruleus of the rat." Microscopy Reseach and Technique. 29. 200-203 (1994)
• [Publications] Sakaguchi,T.: "Expression of basic fibroblast growth factor receptor messenger RNA in the periinfarcted brain tissue." Restorative Neurology and Neuroscience.7. 29-36 (1994)
• [Publications] Mushiake,S.: "Gene for members of the GATA-binding protein family(GATA-GT1 and GATA-GT2) together with H+/K+-ATPase are spesifically transcribed in gastric parietal cells." FEBS Lett.340. 117-120 (1994)
• [Publications] Yuguchi,T.: "Messenger RNA and protein expression of vasic fibroblast growth factor receptor after cortical ablation." Mol. Brain Res.25. 50-56 (1994)
• [Publications] Fujita,M.: "Distribution of cocaine recognition sites in rat brain : in vitro and ex vivo autoradiography with [125I]RTI-55." J. Chem. Neuroanat.7. 13-23 (1994)
• [Publications] Kobayashi,N.: "GAP-43(B50/F1) gene regulation by axonal injury of the hypoglossal nerve in the adult rat." Mol. Brain Res.21. 9-18 (1994)
• [Publications] Ohno,K.: "Occurrence of galanin-like immunoreactivity in vestibular and cochlear efferent neurons after labyrinthectomy in the rat." Brain Res.644. 135-143 (1994)
• [Publications] Otori,Y.: "Marked increase in glutamate-aspartate transporter(GLAST/CluT-1) mRNA following transient retinal ischemia." Mol. Brain Res.27. 310-314 (1994)
• [Publications] Matsumoto,K.: "A novel family of heparin-binding growth factors, pleiotrophin and midkine, is expressed in the developing rat cerebral cortex." Dev. Brain Res.79. 229-241 (1994)
• [Publications] Mushiake,S.: "Two-dimensional demonstration of myenteric nerve plexus : Application for pseudo-hirschsprung's disease." J. of Pediatric Surgery. 29. 1472-1482 (1994)
• [Publications] Matsumoto,K.: "Localization of pleiotrophin and midkine in the postnatal developing cerebellum." Neurosci. Lett.178. 216-220 (1994)
• [Publications] Yamano,M.: "Distribution of corticotropin-releasing factor and calcitonin gene related peptide in the developing mouse cerebellum." Neurosci. Res.19. 387-396 (1994)
• [Publications] Shimizu,H.: "Effect of Dibutyryl Cyclic AMP on Morphologic Features and Marker Production of Human Gervical Argyrophil Small-Cell Carcinoma Cell Line." Int. J. Cancer. 56. 766-771 (1994)
• [Publications] Saika,T.: "Differential regulation of phospholopase Cisozymes in the rat facial nucleus following axotomy." Neurosci.59. 121-129 (1994)
• [Publications] Kondo,E.: "Coexpression of GABAA receptor g1 and g2 subunits in the rat trigeminal ganglion." Mol. Brain Res.21. 363-367 (1994)
• [Publications] Imaizumi,K.: "Differential expression of skg mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury." Mol. Brain Res.26. 189-196 (1994)
• [Publications] Kiyama,H.: "Growth Factors and Extracellular Signal-Rugulated Kinases (Mitogen-Activated Protein Kinase) in the Rat Pineal Gland." Neuroendocrinology. 59. 152-155 (1994)
• [Publications] Ohno,K.: "Up-regulation of GAP-43(B50/F1) gene expression in vestibular efferent neurons following labyrinthectomy in the rat : In situ hybridization using an alkaline phosphatese-labeled probe." Hearing Res.80. 123-127 (1994)
• [Publications] Inoue,K.: "Cloning and expression of a bovine glutamate transporter." Mol. Brain Res.(印刷中). (1995)
• [Publications] Adams,R.H.: "Gene structure and glial expression of the glycine transporter GlyT1 in emryonic and adult rodents." J. Neurosci.(印刷中). (1995)
• [Publications] 川合述史: "分子から見た脳" 講談社, 212 (1994)
• [Publications] Nakano,R.et al.: "A novel mutation in Cu/Zn superoxide dismutase gene in Japanese familial amyotrophic lateral sclerosis" Biochem.Biophys.Res.Commun.(in press). (1994)
• [Publications] Ishida,N.et al.: "Circadian expression of NMDA recptor mRNAs,ε3 and ζ1,in the suprachiasmatic nucleus of rat brain" Neurosci.Lett.(in press). (1994)
• [Publications] Watanabe,M.et al.: "Differential distributions of the NMDA receptor channel subunit mRNAs in the mouse retina." Brain Res.634. 328-332 (1994)
• [Publications] Araki,K.et al.: "Selective expression of the glutamate receptor channel δ2 subunit in cerebellar Purkinje cells." Biochem.Biophtys.Res.Commun.197. 1267-1276 (1993)
• [Publications] Takano,H.et al.: "Chromosomal localization of the ε1,ε3 and ζ1 subunit genes of the human NMDA receptor channel." Biochem.Biophtys.Res.Commun.197. 922-926 (1993)
• [Publications] Yamakura,T.et al.: "Phosphorylation of the carboxyl-terminal domain of the ζ1 subunit is not responsible for potentiation by TPA of the NMDA receptor channel." Biochem.Biophtys.Res.Commun.196. 1537-1544 (1993)
• [Publications] Watanabe,M.et al.: "Distinct distributions of five N-methyl-D-aspartate receptor channel subunit mRNAs in the forebrain." J.Comp.Neurol.338. 377-390 (1993)
• [Publications] Watanabe,M.et al.: "Distinct spatio-temporal distributions of the NMDA receptor channel subunit mRNAs in the brain." Ann.NY Acad.Sci.707. 463-466 (1993)
• [Publications] Kawamoto,S.et al.: "Expression of the α1 and α2 subunits of the AMPA-selective glutamate receptor channel in insect cells using a Baculovirus vector" Ann.NY Acad.Sci.707. 460-462 (1993)
• [Publications] Mishina,M.et al.: "Molecular and functional diversity of the NMDA receptor channel" Ann.NY Acad.Sci.707. 136-152 (1993)
• [Publications] Yamakura,T.et al.: "Different sensitivities of NMDA receptor channel subtypes to noncompetitive antagonists" NeuroReport. 4. 687-690 (1993)
• [Publications] Mori,H.et al.: "Involvement of the carboxyl-terminal region in modulation by TPA of the NMDA receptor channel" NeuroReport. 4. 519-522 (1993)
• [Publications] Tsubokawa,H.et al.: "Block of long-term potentiation by intracellular application of anti-phosphatidylinositol 4,5-bisphosphate antibody in hippocampal pyramidal neurons." Neuroscience. 55. 643-651 (1993)
• [Publications] Miwa,A.et al.: "Presynaptic glutamate receptors depress inhibitory postsynaptic transmission in lobster neuromuscular synapse." J.Neurophysiol.70. 1159-1167 (1993)
• [Publications] Robinson,H.P.C.et al.: "Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons." J.Neurosci.Methods. 46. 157-165 (1993)
• [Publications] Tsubokawa,H.et al.: "Inositol 1,3,4,5-tetrakisphosphate (IP_4) as a mediator of neuronal death in ischemic hippocampus." Neuroscience. (in press).
• [Publications] Shimazaki,K.et al.: "Changes in inositol 1,4,5-triphosphate 3-kinase immunoreactivity following transient ischemia in gerbil hippocampus." NeuroReport. (in press).
• [Publications] Tsubokawa,H.et al.: "Ca^<2+>-dependent non-NMDA receptor-mediated synaptic currents in ischemic CA1 hippocampal neurons." J.Neurophysiol.(in press).
• [Publications] Ozawa,S.and Iino,M.: "Two distinct types of AMPA responses in cultured rat hippocampal neurons" Neuroscience Letters. 115. 187-190 (1993)
• [Publications] Ozawa,S.: "Glutamate receptor channels in hippocampal neurons" Japanese Journal of Physiology. 43. 141-159 (1993)
• [Publications] Bochet,P.et al.: "Subunit composition at the single cell level explains functional properties of a glutamate-gated channel" Neuron. (in press). (1994)
• [Publications] 小澤瀞司: "海馬ニューロンの興奮性シナプス" 神経研究の進歩. 38(1). 23-33 (1994)
• [Publications] Yoshimura,Y & Tsumoto,T.: "Dependence of LTP induction on postsynaptic depolarization:A perforated patch clamp study in visual cortical slices" Journal of Neurophysiology. in press. (1994)
• [Publications] Funauchi,Y.et al.: "Effects of an inhibitor for calcium/calmodulin-dependent protein phosphatase,calcineurin,on induction of long-term potentiation in rat visual cortex" Neuroscience Research. in press. (1994)
• [Publications] Sato,H.et al.: "Broad-tuned chromatic inputs to color-selective neurons in the monkey visual cortex" Journal of Neurophysiology. in press. (1994)
• [Publications] Takahashi,M.P.et al.: "Laminar difference in tetanus-induced increase of intracellular Ca^<2+> in visual cortex of young rats" Neuroscience Research. 17. 217-228 (1993)
• [Publications] Takahashi,M.P.et al.: "Contribution of NMDA receptors to tetanus-induced increase in postsynaptic Ca^<2+> in visual cortex of young rats" Neuroscience Research. 17. 229-239 (1993)
• [Publications] Hata,Y.et al.: "Development of local horizontal interactions in cat visual cortex studied by cross-correlation analysis" Journal of Neurophysiology. 69. 40-56 (1993)
• [Publications] Minakami,R.,Katsuki,F.and Sugiyama,H.: "A variant of metabotropic glutamate receptor subtype 5:an evolutionary conserved insertion with no termination codon" Biochem.Biophys.Res.Commun.194. 622-627 (1993)
• [Publications] Araki,T.,Kenimer,J.,Nishimune,A.,Sugiyama,H.,ら: "Identification of the metabotropic glutamate receptor-1 protein in the rat trigeminal ganglion" Brain Research. 627. 341-344 (1993)
• [Publications] Sugiyama,H.,Nakamura,K.and Nukada,T.: "Mode of interactions between metaborropic glutamate receptors and G proteins in Xenopus ooctye" Annals of NY Academy of Science. 707. 515-518 (1993)
• [Publications] Nakamura,K.,Nukada,T.,Haga,T.& Sugiyama,H.: "G protein-mediated inhibition of phosphoinositide metabolism evoked by metabotropic glutamate receptors in frog oocytes" J.Physiol.(Lond.). 474. 35-41 (1994)
• [Publications] Toru Shida,et.al.: "Expression of muscarinic and nicotinic receptor mINA in the salivary gland of rats;a study by in situ hybridization histochemistry." Molecular Brain Research. 17. 335-339 (1993)
• [Publications] Tatsuya Asai,et al.: "Differential expression of two members of FGF receptor gene family FGFR-1 and FGFR-2 mRNA,in the adult rat central nervous system." Molecular Brain Research. 17. 174-178 (1993)
• [Publications] Gui Lan Yao,et.al.: "Distribution of GAP-43(B50/F1) mRNA in the adult rat brain by in situ hybridization using an alkaline phosphatase labeled probe" Molecular Brain Research. 18. 1-16 (1993)
• [Publications] Hiroshi Maeno,et al.: "Distribution of the substance P receptor (NK-1 receptor) in the central nervous system." Molecular Brain Research. 18. 43-58 (1993)
• [Publications] Emiko Senba,et al.: "Stress-induced c-fos expression in the rat Brain;activation mechanism of sympathetic pathway." Brain Research Bull.31. 329-344 (1993)
• [Publications] Masahiro Fujata,et al.: "Ontogeny of dopamine transporter mRNA expression in the rat brain." Molecular Brain Research. 19. 222-236 (1993)
• [Publications] Takanori Saika,et al.: "Changes in preproenkephalin mRNA after unilateral and bilateral labyrinthectomy in the rat medial vestibular nucleus." Molecular Brain Research. 19. 237-240 (1993)
• [Publications] Hiroshi Kiyama,et al.: "Sympathetic and parasympathetic ganglia express non-NMDA type glutamate receptors;distinct receptor subunit composition in the principle and SIF cells." Molecular Brain Research. 19. 345-348 (1993)
• [Publications] Hiroshi Kiyama,et al.: "Charateristic localization of non-NMDA type glutamate receptor subunits in the rat pituitary gland." Molecular Brain Research. 19. 262-268 (1993)
• [Publications] Tatsuo Furuyama,et al.: "Region-specific expression of subunits of ionotropic glutamate receptors(AMPA-type,KA-type and NMDA receptors)in the rat spinal cord with special reference to nociception." Molecular Brain Research. 18. 141-151 (1993)
• [Publications] Akio Wanaka,et al.: "Developmentally regulated expressio of pleiotrophin,a novel heparin binding growth factor,in the nervous system of the rat." Developmental Brain Research. 72. 133-144 (1993)
• [Publications] Mariko Yamano,et al.: "The innervation of calcitonin gene-related peptide to the Purkinje cells and granule cells in the developing mouse cerebellum" Developmental Brain Research. 72. 107-117 (1993)
• [Publications] Koji Sato,et al.: "The differential expression patterns of messenger RNAs encoding non-N-methyl-D-asparatate glutamate receptor subunits(Glurl-4) in the rat brain." Neuroscience. 52. 515-539 (1993)
• [Publications] Masahiro Fujita,et al.: "Cellular localization of serotonin transporter mRNA in the rat brain." Neuroscience Letters. 162. 59-62 (1993)
• [Publications] Furuta,Y.et al.: "MDS-like experimental myelodysplasia:multilineage abnormal hematopoiesis in transgenic mice harbaring the SV40 large T antigen under an immunoglobulin" Exp.Hematol.21. 806-815 (1993)
• [Publications] Nada,S.et al.: "Constitutive activation of Src family kinases in mouse embryos that lack Csk" Cell. 73. 1125-1135 (1993)
• [Publications] Imoto,S.et al.: "Regulation of class II NHC gene expression by the inducible antisense RNA in transgenic mice" Anal.Biochem.210. 231-234 (1993)
• [Publications] Furuta,Y.et al.: "Degeneration of skeletal and cardiac muscles in c-myb-transgenic mice" Transgenic Res.2. 199-207 (1993)
• [Publications] Yagi,T.et al.: "A novle negative selection for homologous recombinants using diphtheria toxin A franment gene" Anal.Biochem.214. 77-86 (1993)
• [Publications] Yagi,T.et al.: "A novel ES cell strain,TT2,with high germline-differentiating potency" Anal.Biochem.214. 68-76 (1993)
• [Publications] Yagi,T.et al.: "Regional localization of Fyn in adult brain:Studies with mice in which fyn gene was replaced by lacZ" Oncogene. 8. 3343-3351 (1993)
• [Publications] Tsukada,T.et al.: "Enhanced proliferative potential in culture of cells from P53-deficient mice" Oncogene. 8. 3313-3322 (1993)
• [Publications] Yagi,T.et al.: "A role for Fyn tyrosine kinase in the suckling behavior of neonatal mice" Nature. 366. 742-745 (1993)
• [Publications] 中村健司 他: "自在な標的遺伝子置換法" 実験医学. 11(20). 138-141 (1993)
• [Publications] 権藤洋一他: "トランスジェニックマウスを用いた変異原の高感度解析法の開発" 環境変異原研究. 15. 39-49 (1993)
• [Publications] Gondo,Y.et al.: "High-frequency genetic reversion mediated by a DNA duplication:Mouse pink-eyed unstable mutation" Proc.Natul.Acad.Sci.U.S.A.90. 297-301 (1993)
• [Publications] Kawai,N.& Nakajima,T.: "Natural and Synthetic Neurotoxins (ed.by A.Harvey)" Academic Press, 27(319-345) (1993)
• [Publications] Kawai,N.: "Aspects of synaptic transmission (ed.by T.W.Stone)" Taylor & Francis, 10(221-230) (1993)
• [Publications] 杉山博之: "「生体における情報伝達」(分担執筆)" 南江堂(西塚泰美・田中千賀子 編集), 322 (1993)
• [Publications] 伊藤功,杉山博之: "「レセプター ----基礎と臨床----」(分担執筆)" 朝倉書店(井村裕夫・岡哲雄・芳賀達也・岸本英爾 編集), 944 (1993)
• [Publications] Sakimura,K.,et al.: "Primary sructure and expression of the γ2 subunit of the glutamate reutamate receptor channel selective for kainate." Neuron. 8. 267-274 (1992)
• [Publications] Morita,T.,et al.: "Cloning and functional expression of cDNA encoding the mouse β2 subunit of the kainate-selective glutamate receptor channel." Mol.Brain Res.14. 143-146 (1992)
• [Publications] Yamazaki,M.,et al.: "Molecular cloning of a cDNA encoding a novel member of the mousr glutamate receptor channel family." Biochem.Biophys.Res.Commun.183. 886-892 (1992)
• [Publications] Yamazaki,M.,et al.: "Cloning,expression and modulation of a mouse NMDA receptor subunit." FEBS Lett.300. 39-45 (1992)
• [Publications] Meguro,H.,et al.: "Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs." Nature. 357. 70-74 (1992)
• [Publications] Kutsuwada,T.,et al.: "Molecular diversity of the NMDA receptor channel." Nature. 358. 36-41 (1992)
• [Publications] Mori,H.,et al.: "Identification by mutagenesis of a Mg^<2+> block site of the NMDA receptor channel." Nature. 358. 673-675 (1992)
• [Publications] Uchino,S.,et al.: "Mutations in a putative agonist binding region of the AMPA-selective glutamate receptor channel." FEBS Lett.308. 253-257 (1992)
• [Publications] Morita,T.,et al.: "Synaptocanalin I,a protein associated with brain ω-conotoxin-sensitive calcium channesl." Biomed.Res.13. 357-364 (1992)
• [Publications] Ikeda,K.,et al.: "Cloning and expression of the ε4 subunit of the NMDA receptor channel." FEBS Lett.313. 34-38 (1992)
• [Publications] Watanabe,M.,et al.: "Developmental changes in distribution of the NMDA receptor channel subunit mRNAs in the brain." NeuroReport. 3. 1138-1140 (1992)
• [Publications] Shimazaki,K.,et al.: "Purification of AMPA type glutamate receptor by a spider toxin." Mol.Brain Res.13. 331-337 (1992)
• [Publications] Tsubokawa,H.,et al.: "Abnormal Ca^<2+> homeostasis before cell death revealed by whole cell recording of ischemic CA1 hippocampal neurons." Neurosci.49. 807-817 (1992)
• [Publications] Kirino,T.,et al.: "Disturbance of membrane function proceding ischemic delayed neuronal death in the gerbil hippocampus." F.Cereb.Blood Flow Metab.12. 408-417 (1992)
• [Publications] Ishida,A.,et al.: "Ischemia-induced changes in Pip_2 levels of gerbil hippocampus." Neurosci.Res.15. 305-309 (1992)
• [Publications] Tsuzuki,K.,et al.: "Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam." Mol.Brain Res.16. 105-110 (1992)
• [Publications] Ozawa,S.: "Glutamate receptor channels in hippocampal neurons." Japanese Journal of Physiology.(1993)
• [Publications] Tamura,H.et al.: "Activity-dependent potentiation and depression of visual cortical responses to potic nerve stimulation in kittens." Journal of Neurophysiology. 68. 1603-1612 (1992)
• [Publications] Funauchi,M.et al.: "Long-term depression is induced in Ca2+/ calmodulin kinase-inhibited neurons in visual cortex." NeuroRoport. 3. 173-176 (1992)
• [Publications] Tsumoto,T.: "Long-term potentiation and long-term depression in the neocortex." Progress in Neurobiology. 39. 209-228 (1992)
• [Publications] Hata,Y.et al.: "Development of local horizontal interactions in cat visual cortex studied by cross-correlation analysis." Journal of Neurophysiology. 69. 40-56 (1993)
• [Publications] Minakami.R.,et al.: "Postnatal development of mRNA specific for a metabotropic glutamate receptor in the rat brain." Neurosci.Res.15. 58-63 (1992)
• [Publications] Ito,I.,et al.: "3,5-Dihydroxyphenylglycine:A potent agonist of metabotropic glutamate receptors." NeuroReport. 3. 1013-1016 (1992)
• [Publications] Shimano,H.et al: "Plasma Lipoprotein metabolism in transgenic mice overexpressing apolipo- protein E:Accelerated clearance of lipoproteins containing apolipoprotein B." J.Clin.Invest.90. 2084-2091 (1992)
• [Publications] Sasaoka,T.et al: "Analysis of the human tyrosine hydroxylase promoter-chloramphenicol acetyltransferase chimeric gene expression in transgenic mice." Mol.Brain Res.16. 274-286 (1992)
• [Publications] Abeliovich,A.et al: "On somatic recombination in the central nervous system of transgenic mice." Science. 257. 404-408 (1992)
• [Publications] Takagi,K.et al: "A rapid and efficient protocol of the inverted PCR using two primer pairs." Biotechniques. 13. 176-178 (1992)
• [Publications] Izawa,M.et al: "Inhibition of chemical carcinogenesis in vivo by azatyrosine." Cancer Res.52. 1628-1630 (1992)
• [Publications] Kobayashi,K.et al: "Genetic alteration of catecholamine specificity in transgenic mice" Proc Natl Acad Sci USA. 89. 1631-1635 (1992)
• [Publications] Araki,T.,et al.: "Localization of GABA -receptor γ_2 subunit mRNA contain-ing neurons in the ra^^At central nervous system." Neuroscience. 47. 45-61 (1992)
• [Publications] Sato,M.,et al.: "Different postnatal development of cells expressing mRNA encoding neurotensin receptor." Neuroscience. 48. 137-149 (1992)
• [Publications] Araki,T.,et al.: "The GABA a receptor γ_1 subunit is expressed by distinct neuronal populations." Mol.Brain Res.15. 121-132 (1992)
• [Publications] Sato,K.,et al.: "Regional distribution of cells expressing glycine receptor α_2 subunit mRNA in the rat brain." Brain Res.590. 95-108 (1992)
• [Publications] Araki,T.,et al.: "GABA receptor subunit messenger RNAs show differential expre^^Assion during cortical development in the rat brain." Neuroscience. 51. 583-591 (1992)
• [Publications] Minakami,R.,et al.: "Postnatal development of mRNA specific for a metabotro-pic glutamate receptor in the rat brain." Neurosci.Res.15. 58-63 (1992)
• [Publications] N.Kawai,et al.eds.: "Neuroreceptors,Ion Channels and the Brain" Elsevier, 234 (1992)