遺伝子改変マウスの高速表現型解析のための全自動8ノ字型迷路課題の確立

• Project/Area Number: 19653081
• Research Category: Grant-in-Aid for Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Experimental psychology
• Research Institution: Kyoto University
• Principal Investigator: 宮川 剛 Kyoto University, 医学研究科, グループリーダー (10301780)
• Co-Investigator(Kenkyū-buntansha): 高雄 啓三 京都大学, 医学研究科, 客員研究員 (80420397)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,300,000 (Direct Cost: ¥3,300,000); Fiscal Year 2008: ¥1,300,000 (Direct Cost: ¥1,300,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: 遺伝子改変マウス / 行動解析 / 作業記憶 / 精神疾患 / スクリーニング / 遺伝子 / 行動実験

Research Abstract

一般的遺伝子改変マウスによく用いられているC57BL/6Jのマウスを用い、全自動8ノ字型迷路課題で標準プロトコルとして適切な各種パラメーターを決定するための実験を行った。遅延交替課題では、遅延なしで十分な正答率(80%以上)が得られるようになった後、遅延の長さを変化させ、遅延の長短の正答率への影響を検討した。遅延交替課題とは、ラットやマウスなどの齧歯類で古典的に用いられている作業記憶課題である。マウスはまず出発箱(Start Box)に入れられ、次に、左右の走路のうちどちらか一方に強制的に誘導される(強制選択;Forced Choice)。餌を取得後、自ら走路を走り、出発箱に戻る。出発箱と左右の走路へのドアが開き、左右の走路のうちどちらかを自由に選ぶことができる(自由選択;Free Choice)。この時、直前の強制選択で選択させられた走路と逆側の走路を選択すると正解で餌をもらうことができるが(Correct Choice)、同じ走路を選択すると誤反応となり餌はもらえず、一定時間、拘束される(Incorrect Choice)。この後、自ら走路を走り、出発箱に戻る。この手続きが10回ほど繰り返されるが、強制選択の走路は、毎回、擬ランダムに変化する。強制選択後に出発箱に戻ってから、出発箱のドアが開くまでの遅延時間を操作することにより、課題の難易度を操作することができるが、この遅延時間の効果を詳細に検討した。通常の訓練試行では3秒の遅延時間としているが、それを10秒、30秒、60秒と延長したところ、遅延時間依存的に課題の難易度が増し、正答率は低下していった。全自動8ノ字型迷路課題は、遺伝子改変マウスの作業記憶のスクリーニング方法としても非常に有効であると考えられる。

Research Products

• [Journal Article] Smaller dendritic spines, weaker synaptic transmission but enhanced spatial learning in mice lacking shankl (2008)
  • Author(s): Hung, AY., Futai, K., Sala, C., Valtschanoff, JG., Ryu, J., Burgoon, M., Kidd, FL., Sung, CC., Miyakawa, T., Bear, MF., Weinberg, RJ., Sheng, M
  • Journal Title: Journal of Neuroscience 28(7) Pages: 1697-1708
  • Peer Reviewed
• [Journal Article] Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2. (2008)
  • Author(s): Sano, H., Nagai, Y., Miyakawa, T., Shigemoto, R., Yokoi, M
  • Journal Title: Journal of Neurochemistry 105 Pages: 546-556
  • Peer Reviewed
• [Journal Article] Increased anxiety-like behavior in neuropsin (kallikrein-related peptidase 8) gene-deficient mice (2008)
  • Author(s): Horii, Y., Yamasaki, N., Miyakawa, T., Shiosaka, S
  • Journal Title: Behavioral Neuroscience 122(3) Pages: 498-504
  • Peer Reviewed
• [Journal Article] Down-regulation of protocadherin-_, A isoforms in mice changes contextual fear conditioning and spatial working memory (2008)
  • Author(s): Fukuda, E., Hamada, S., Hasegawa, S., Katori, S., Sanbo, M., Miyakawa, T., Yamamoto, T., Yamamoto, H., Hirabayashi, T., Yagi, T
  • Journal Title: European Journal of Neuroscience 28(7) Pages: 1362-76
  • Peer Reviewed
• [Journal Article] Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants (2008)
  • Author(s): Sakae, N., Yamasaki, N., Kitaichi, K., Fukuda, T, Yamada, M., Yoshikawa, H., Hiranita, T., Tatsumi, Y., Kira, J., Yamamoto, T., Miyakawa, T., Nakayama, KI
  • Journal Title: Human Molecular Genetics 17(20) Pages: 3191-203
  • Peer Reviewed
• [Journal Article] Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia (2008)
  • Author(s): Ikeda, M., Hikita, T., Taya, S., Uraguchi-Asaki, J., Toyo-oka, K., Wynshaw-Boris, A., Ujike, H., Inada, T., Takao, K., Miyakawa, T., Ozaki, N., Kaibuchi, K., Iwata, N
  • Journal Title: Human Molecular Genetics 17(20) Pages: 3212-22
  • Peer Reviewed
• [Journal Article] Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain (2008)
  • Author(s): Imayoshi, I., Sakamoto, M., Ohtsuka, T., Takao, K., Miyakawa, T., Yamaguchi, M., Mori, K., Ikeda, T., Itohara, S., Kageyama, R
  • Journal Title: Nature Neuroscience 11(10) Pages: 1153-61
  • Peer Reviewed
• [Journal Article] Mice lacking the kf-1 gene exhibit increased anxiety- but not despair-like behavior (2008)
  • Author(s): Tsujimura, A., Matsuki, M., Takao, K., Yamanishi, K., Miyakawa, T., Hashimoto-Gotoh, T
  • Journal Title: Frontiers in Behavioral Neuroscience 2 Pages: 4-4
  • Peer Reviewed
• [Journal Article] Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders (2008)
  • Author(s): Yamasaki, N., Maekawa, M., Kobayashi, K., Kajii, Y., Maeda, J., Soma, M., Takao, K., Tanda, K., Ohira, K., Toyama, K., Kanzaki, K., Fukunaga, K., Sudo, Y., Ichinose, H., Ikeda, M., Iwata, N., Ozaki, N., Suzuki, H., Higuchi, M., Suhara, T., Yuasa, S., Miyakawa, T
  • Journal Title: Molecular Brain 1 Pages: 6-6
  • Peer Reviewed
• [Journal Article] Comprehensive behavioral phenotyping of calpastatin-knockout mice (2008)
  • Author(s): Nakajima, R., Takao, K., Huang, SM., Takano, J., Iwata, N., Miyakawa, T., Saido, TC
  • Journal Title: Molecular Brain 1 Pages: 7-7
  • Peer Reviewed
• [Journal Article] Impaired long-term memory retention and working memory in sdymutant mice with a deletion in Dtnbpl, a susceptibility gene for schizophrenia (2008)
  • Author(s): Takao, K., Toyama, K., Nakanishi, K., Hattori, S., Takamura, H., Takeda, M., Miyakawa, T., Hashimoto, R
  • Journal Title: Molecular Brain 1 Pages: 11-11
  • Peer Reviewed
• [Journal Article] Normal mitochondrial respiratory function is essential for spatial remote memory in mice (2008)
  • Author(s): Tanaka, D., Nakada, K., Takao, K., Ogasawara, E., Kasahara, A., Sato, A., Yonekawa, H., Miyakawa, T., Hayashi, J
  • Journal Title: Molecular Brain 1 Pages: 21-21
  • Peer Reviewed
• [Journal Article] Smaller Dendritic Spines, Weaker Synaptic Transmission but Enhanced Spatial Learning in Mice Lacking Shank1 (2008)
  • Author(s): Hung, AY., Futai, K., Sala, C., Valtschanoff, JG., Ryu, J., Burgoon, M., Kidd, FL., Sung, CC., Miyakawa, T., Bear, MF., Weinberg, RJ., and Sheng, M.
  • Journal Title: Journal of Neuroscience 28(7) Pages: 1697-1708
  • Peer Reviewed
• [Journal Article] Increased social interaction in mice deficient of the striatal medium spiny neuron-specific phosphodiesterase 10A2 (2008)
  • Author(s): Sano, H., Nagai, Y., Miyakawa, T., Shigemoto, R., Yokoi, M.
  • Journal Title: Journal of Neurochemistry (in press)
  • Peer Reviewed
• [Journal Article] Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi (2007)
  • Author(s): Hattori, S., Hashimoto, R., Miyakawa, T., Yamanaka, H., Maeno, H., Wada, K., Kunugi, H.
  • Journal Title: Behavioural Brain Research 180(1) Pages: 69-76
  • Peer Reviewed
• [Journal Article] Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion. (2007)
  • Author(s): Shibata, M., Yamasaki, N., Miyakawa, T., Ohtani, R., Ihara, M., Takahashi, R., and Tomimoto, H
  • Journal Title: Stroke 38(10) Pages: 2826-2832
  • Peer Reviewed
• [Journal Article] Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and non-motoneuronal phenotypes. (2007)
  • Author(s): Niemann, S., Kanki, H., Fukui, Y., Takao, K., Fukaya, M., Hynynen, MN., Churchill, MJ., Shefner, JM., Bronson, RT., Watanabe, M., Brown, RH, Jr., Miyakawa, T., Itohara, S., Hayashi, Y.
  • Journal Title: European Journal of Neuroscience 26(6) Pages: 1407-1420
  • Peer Reviewed
• [Journal Article] Altered sensitivities to morphine and cocaine in scaffold protein tamalin knockout mice (2007)
  • Author(s): Ogawa, M., Miyakawa, T., Nakamura, K., Kitano, J., Furushima, K., Kiyonari, H., Nakayama, R., Nakao, K., Moriyoshi, K., Nakanishi, S.
  • Journal Title: Proc Natl Acad Sci USA 104(37) Pages: 14789-94
  • Peer Reviewed
• [Presentation] Alpha-CaMK IIヘテロノックアウトにより引き起こされる行動異常と未成熟歯状回 (2008)
  • Author(s): 宮川剛
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Factor analyses of large-scale data justify the behavioral test battery strategy to reveal the functional significances of the genes expressed in the brain (2007)
  • Author(s): Miyakawa, T., Yamasaki, N., Tanda, K., Toyama, K. and Takao, K.
  • Organizer: 7th IBRO World Congress of Nuroscience
  • Place of Presentation: Melbourne, Australia
• [Presentation] Alpha-CaMK II deficiency causes abnormal behaviours related to schizophrenia and other psychiatric disorders (2007)
  • Author(s): Yamasaki, N., Kajii, Y., Takao, K., Kanzaki, K., Ikeda, M., Iwata, N., Ozaki, N., and Miyakawa, T.
  • Organizer: 7th IBRO World Congress of Nuroscience
  • Place of Presentation: Melbourne, Australia
• [Presentation] The dentate gyrus of alpha-CaMK II deficient mice is morphologically and histologically immature (2007)
  • Author(s): Takao, K., Maekawa, M., Maeda, J., Soma, M., Higuchi, M., Suhara, T., Yuasa, S., and Miyakawa, T.
  • Organizer: 7th IBRO World Congress of Nuroscience
  • Place of Presentation: Melbourne, Australia
• [Presentation] Alpha-CaMK II deficiency causes dysregulated behaviours and immature dentate gyrus (2007)
  • Author(s): Miyakawa, T.
  • Organizer: International Conference of Neurons and Brain Disease
  • Place of Presentation: Toronto, Canada
• [Presentation] 遺伝子改変マウスの体系的な脳行動表現型解析と精神神経疾患研究 (2007)
  • Author(s): 宮川剛
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会 合同大会
  • Place of Presentation: 横浜
• [Presentation] Schnurri-2欠失マウスの精神疾患様行動異常 (2007)
  • Author(s): 高雄啓三、山崎信幸、高木豪、石井俊輔、宮川剛
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会 合同大会
  • Place of Presentation: 横浜
• [Presentation] alpha-CaMK IIヘテロノックアウトにより引き起こされる行動異常と未成熟歯状回 (2007)
  • Author(s): 山崎信幸、前川素子、小林克典、梶井靖、前川純、相馬美歩、高雄啓三、神崎康治、鈴木秀典、樋口真人、須原哲也、湯浅茂樹、宮川剛
  • Organizer: 第30回日本神経科学大会、第50回日本神経化学会大会、第17回日本神経回路学会大会 合同大会
  • Place of Presentation: 横浜
• [Presentation] Alpha-CaMk II deficiency causes dysregulated behaviors and immature dentate gyrus (2007)
  • Author(s): Yamasaki, N., Maekawa, M., Kobayashi, K., Kajii, Y., Maeda, J., Takao, K., Ohira, K., Tanda, K., Ohsako, S., Toyama, K., Higuchi, M., Fukunaga, K., Sudo, Y., Ichinose, H., Ikeda, M., Iwata, N., Ozaki, N., Suhara, T., Suzuki, H., Yuasa, S., Miyakawa, T.
  • Organizer: Society for Neuroscience 37th Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] Deletion of Schnurri-2 causes multiple behavioral abnormalities related to psychiatric disorders in mic (2007)
  • Author(s): Takao, K., Yamasaki, N., Takagi, T., Ishii, S., Miyakawa, T.
  • Organizer: Society for Neuroscience 37th Annual Meeting
  • Place of Presentation: San Diego, USA
• [Presentation] Alpha-CaMk II deficiency causes dysregulated behaviors and immature dentate gyrus (2007)
  • Author(s): 宮川剛
  • Organizer: 第30回日本分子生物学会年会 第80回日本生化学会大会合同大会 BMB2007
  • Place of Presentation: 横浜