臺灣博碩士論文加值系統

本論文的主要目的在探討大白鼠海馬迴和空間學習與記憶形成相關的基因表現，藉由莫氏水迷津學習試驗 (Morris water maze learning task) 篩選學習快 (在第三個學習區段內，即可在三十秒內找到平台) 和學習慢 (第七或第八個學習區段才可在三十秒內找到平台) 的大白鼠，抽取其海馬迴的總核糖核酸 (total RNA)，以聚合酶連鎖反應差異顯示法 (PCR differential display) 進行比較。經全部使用二百四十組引子配對的篩選後，總共發現有九十八個互補去氧核糖核酸片段 (complementary DNA，簡稱cDNA) 的含量具有顯著差異。經由選殖 (cloning) 並定序分析結果得知其中之一與大白鼠血清及糖皮質素誘導激酶 (serum and glucocorticoid-inducible kinase，簡稱sgk) 基因有百分之九十六的相似性。進一步使用北方墨點法 (Northern blot) 分析後得知，學習快的大白鼠其sgk訊息核糖核酸 (messerger RNA，簡稱mRNA) 的表現量約為學習慢的大白鼠的四倍左右。而在原位雜交法 (in situ hybridization) 的結果顯示，在學習快大白鼠的海馬迴CA1、CA3和齒狀迴 (dentate gyrus) 這三個區域的sgk訊息核糖核酸表現量都有顯著的增加。為更進一步探討sgk在海馬迴中在學習與記憶歷程所扮演的角色，我們利用選殖技術找出sgk的全長互補去氧核糖核酸 (full length cDNA)，再利用定位突變法 (site-directed mutagenesis) 使其在第422個胺基酸的磷酸化位置產生突變，進而喪失活性，再分別將sgk野生型基因和sgk突變型基因轉染 (transfection) 進入大白鼠海馬迴CA1區域後，觀察大白鼠在莫氏水迷津學習試驗的行為表現。結果顯示轉染sgk突變型基因的大白鼠對水迷津的學習顯著變差；相反地，轉染sgk野生型基因的大白鼠對水迷津的學習則會顯著變好。為瞭解學習快和學習慢的大白鼠海馬迴中sgk基因表現量的差異是導因於先天上的差異或後天學習過程所造成，便由任意挑選十隻未經訓練的大白鼠海馬迴組織，經反轉錄聚合酶連鎖反應 (reverse transcription PCR，簡稱RT-PCR) 定量分析結果顯示，大白鼠海馬迴sgk訊息核糖核酸在先天上的差異均在百分之四十之內，故可知sgk的基因表現量差異乃是經由學習過程所造成。另一方面，由可見式平台水迷津學習試驗結果得知，在學習快和學習慢的大白鼠，以及海馬迴轉染載體與sgk突變型基因的大白鼠，均不是因為其視覺區辨能力 (visual discrimination)、運動協調性 (motor coordination) 以及動機狀態 (motivational state) 等因素，而導致其在莫氏水迷津學習試驗中產生差異。這些結果更進一步證明了sgk基因表現量的改變是因為學習過程所造成的。
綜合以上的結果得知，在空間學習與記憶形成過程中，會有不同的基因表現參與此歷程，而sgk便是其中之一。本論文的結果不僅是第一個，而且具有最直接的證據證明增加sgk的基因表現會顯著促進空間學習與記憶的穩固作用 (consolidation)。另一方面，本論文的結果也對糖皮質誘導記憶穩固的分子機制提供了一個新的詮釋。

By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are differentially expressed between the fast learners and slow learners in the Morris water maze learning task. One of these cDNA fragments encodes the rat serum- and glucocorticoid-inducible kinase (sgk) gene. Northern blot analysis revealed that the sgk mRNA level was approximately four-fold higher in the hippocampus of fast learners than slow learners. In situ hybridization results indicated that sgk mRNA level was markedly increased in CA1, CA3 and dentate gyrus of hippocampus in fast learners. Transient transfection of the sgk mutant DNA to the CA1 area significantly impaired, while transfection of the sgk wild-type DNA markedly facilitated water maze performance in rats. These results provide the first and direct evidence that enhanced sgk expression facilitates memory consolidation of spatial learning in rats. These results also elucidate the molecular mechanism of glucocorticoid-induced memory facilitation in mammals.

正文目錄
第一章 緒論……………………………………………………………………1
第一節 學習與記憶 …………………………………………………………2
一、學習與記憶的定義 ……………………………………………………2
二、學習與記憶的表徵 ……………………………………………………3
三、學習與記憶以及突觸的關係 …………………………………………6
第二節 海馬迴 ………………………………………………………………9
一、海馬迴的結構與神經路徑 ……………………………………………9
二、海馬迴與學習記憶的關係……………………………………………12
三、海馬迴與記憶的穩固作用……………………………………………16
四、海馬迴的長期增益作用………………………………………………17
第三節 血清及糖皮質素誘導激酶…………………………………………19
一、血清及糖皮質素誘導激酶─糖皮質素誘發的基因…………………19
二、血清及糖皮質素誘導激酶基因的調控………………………………20
三、血清及糖皮質素誘導激酶的表現與作用……………………………20
四、血清及糖皮質素誘導激酶的異構型…………………………………21
第四節 皮質類固醇…………………………………………………………23
一、皮質類固醇與皮質類固醇受體………………………………………23
二、皮質類固醇調控基因表現的分子機制………………………………24
三、皮質類固醇與學習記憶的關係………………………………………27
第五節 本論文之目的與策略………………………………………………29
第二章 材料與方法 …………………………………………………………33
第一節 實驗動物……………………………………………………………34
第二節 水迷津學習試驗……………………………………………………34
一、實驗儀器………………………………………………………………34
二、隱藏式平台水迷津學習試驗…………………………………………34
三、可見式平台水迷津學習試驗…………………………………………36
第三節 組織解剖……………………………………………………………37
第四節 總核糖核酸的抽取…………………………………………………37
一、抽取總核糖核酸………………………………………………………37
二、去氧核糖核酸酶處理…………………………………………………38
三、總核糖核酸之定量……………………………………………………39
第五節 聚合酶連鎖反應差異顯示法………………………………………39
一、反轉錄反應……………………………………………………………40
二、聚合酶連鎖反應………………………………………………………40
第六節 互補去氧核糖核酸選殖……………………………………………42
一、cDNA片段回收、再複製作用和接合作用……………………………42
二、勝任細胞製備和轉形作用……………………………………………44
三、篩選……………………………………………………………………46
第七節 去氧核糖核酸定序分析……………………………………………49
第八節 北方墨點法…………………………………………………………50
一、核糖核酸洋菜膠電泳…………………………………………………50
二、膜轉漬…………………………………………………………………51
三、預雜交反應……………………………………………………………52
四、探針的製備……………………………………………………………53
五、雜交反應………………………………………………………………55
六、後雜交反應……………………………………………………………55
第九節 原位雜交法…………………………………………………………55
一、玻片的製備……………………………………………………………55
二、冷凍切片………………………………………………………………56
三、腦組織切片的製備……………………………………………………56
四、預雜交反應……………………………………………………………57
五、探針的製備……………………………………………………………57
六、雜交反應………………………………………………………………58
七、後雜交反應……………………………………………………………59
八、資料分析………………………………………………………………59
第十節 質體去氧核糖核酸建立……………………………………………60
一、全長互補去氧核糖核酸選殖…………………………………………60
二、定位突變法……………………………………………………………61
第十一節 海馬迴內基因轉染作用…………………………………………63
一、立體定位手術與埋管…………………………………………………63
二、DNA/PEI製備 …………………………………………………………63
三、海馬迴CA1區域注射 …………………………………………………64
第十二節 免疫組織化學染色法……………………………………………65
一、組織切片的製備………………………………………………………65
二、免疫組織化學染色……………………………………………………65
第十三節 反轉錄聚合酶連鎖反應…………………………………………66
一、反轉錄反應……………………………………………………………66
二、聚合酶連鎖反應………………………………………………………67
三、聚丙醯胺電泳膠分析…………………………………………………68
第十四節 統計分析…………………………………………………………68
一、北方墨點法與原位雜交法的結果分析………………………………68
二、水迷津學習試驗的結果分析…………………………………………68
第三章 結果 …………………………………………………………………70
第一節 莫式水迷津學習試驗篩選在空間學習記憶具有差異性的大白鼠71
第二節 聚合酶連鎖反應差異顯示法篩選與空間學習記憶有關的基因…72
第三節 選殖具有差異的互補去氧核糖核酸片段和定序分析……………73
第四節 北方墨點法確認sgk訊息核糖核酸在大白鼠海馬迴的含量 ……74
第五節 原位雜交法定量sgk基因的訊息核糖核酸在海馬迴中的分佈 …75
第六節 野生型與突變型sgk基因的表現和莫式水迷津學習試驗的關係 75
第七節 sgk訊息核糖核酸的表現和學習的關係 …………………………77
第八節 可見式平台水迷津學習試驗和大白鼠學習快慢以及sgk基因轉染
作用間的關係………………………………………………………78
第四章 討論 …………………………………………………………………81
第五章 結論 …………………………………………………………………90
第六章 參考文獻……………………………………………………………109
附錄
附圖目錄
圖1、莫式水迷津學習試驗所使用的水迷津 ………………………………93
圖2、莫式水迷津學習試驗篩選在空間學習記憶具有差異性的大白鼠 …94
圖3、聚合酶連鎖反應差異顯示法篩選與空間學習記憶有關的基因 ……95
圖4、A48-1-6 互補去氧核糖核酸片段與大白鼠sgk基因的比對…………96
圖5、大白鼠sgk基因全長互補去氧核糖核酸序列…………………………97
圖6、北方墨點法確認sgk訊息核糖核酸在大白鼠海馬迴的含量…………98
圖7、原位雜交法定量sgk基因的訊息核糖核酸在海馬迴中的分佈………99
圖8、帶有紅血球凝集素抗原決定位的質體(HA-SGK)……………………100
圖9、大白鼠海馬迴CA1轉染sgk基因後在莫式水迷津學習試驗的表現…101
圖10、免疫組織化學染色法偵測大白鼠海馬迴CA1區域轉染sgk基因後的
分佈情形 ……………………………………………………………102
圖11、反轉錄聚合酶連鎖反應定量分析之標準曲線圖 …………………103
圖12、反轉錄聚合酶連鎖反應定量分析之標準曲線圖 …………………104
圖13、反轉錄聚合酶連鎖反應定量分析大白鼠海馬迴中sgk訊息核糖核酸
含量 …………………………………………………………………105
圖14、可見式平台水迷津學習試驗和大白鼠學習快慢間的關係 ………106
圖15、可見式平台水迷津學習試驗和sgk基因轉染作用間的關係………107
圖16、糖皮質素誘發大白鼠空間學習記憶形成的分子模式示意圖 ……108
表目錄
表1、選殖具有差異的互補去氧核糖核酸片段和定序分析 ………………92

Abdallah, B., Hassan, A., Benoist, C., Goula, D., Behr, J. P. and Demeneix, B. A. A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyethylenimine. Human Gene Ther. 7, 1947-1954, 1996.
Ahima, R. S. and Harlan, R. E. Differential corticosteroid regulation of type II glucocorticoid receptor-like immunoreactivity in the rat central nervous system: topography and implications. Endocrinology 129, 226-236, 1991.
Alkon, D. L. and Nelson, T. J. Specificity of molecular changes in neurons involved in memory storage. FASEB J. 4, 1567-1576, 1990.
Alliston, T. N., Maiyar, A. C., Buse, P., Firestone, G. L. and Richards, J. S. Follicle stimulating hormone-regulated expression of serum/glucocorticoid- inducible kinases in rat ovarian granulosa cells: a functional role for the sp-1 family in promoter activity. Mol. Endocrinol. 11, 1934-1949, 1997.
Alliston, T. N., Gonzalez-Robayna, I. J., Buse, P., Firestone, G. L. and Richards, J. S. Expression and localization of serum/glucocorticoid-induced kinase in the rat ovary: relation to follicular growth and differentiation. Endocrinology 141, 385-395, 2000.
Amaral, D. G. and Kurz, J. An analysis of the origins of the cholinergic and noncholinergic septal projections to the hippocampal formation of the rat. J. Comp. Neurol. 240, 37-59, 1985.
Amaral, D. G. Memory: Anatomical organization of candidate brain regions. in: Handbook of Physiology. Section I. The Nervous System, Vol 5. Higher Function of the Brain, Part I. edited by Mountcastle, V. B., Plum, F. and Geiger, S. R., MD: Williams and Wilkins, Baltimore, 1987, pp. 211-294.
Amaral, D. G. and Witter, M. P. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571-591, 1989.
Amaral, D. G. and Witter, M. P. Hippocampal formation. in: The Rat Nervous System. edited by George, P., Academic Press, San Diego, 1995, pp. 443-493.
Ariza, J. L., Weinberger, C., Cerelli, G., Glaser, T. M., Handelin, B. L., Housman, D. E. and Evans, R. M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237, 268-275, 1987.
Aronsson, M., Fuxe, K. and Dong, Y. Localization of glucocorticoid receptor mRNA in the male rat brain by in situ hybridization. Proc. Natl. Acad. Sci. USA 85, 9331-9335, 1988.
Bannerman, D. M., Good, M. A., Butcher, S. P., Ramsay, M. and Morris, R. G. M. Distinct components of spatial learning revealed by prior training and NMDA receptor blockade. Nature 378, 182-186, 1995.
Beato, M., Herrlich, P. and Schutz, G. Steroid hormone receptors: many actors in search of a plot. Cell 83, 851-857, 1995.
Bell, L. M., Leong, M. L., Kim, B., Wang, E., Park, J., Hemmings, B. A. and Firestone, G. L. Hyperosmotic stress stimulates promoter activity and regulates cellular utilization of the serum- and glucocorticoid-inducible protein kinase (Sgk) by a p38 MAPK-dependent pathway. J. Biol. Chem. 275, 25262-25272, 2000.
Bingman, V. P., Ioale, P., Casini, G. and Bagnoli, P. Dorsomedial forebrain ablations and home loft association behavior in homing pigeons. Brain Behav. Evol. 26, 1-9, 1985.
Black, J. E. and Greenough, W. T. Developmental approaches to the memory process. in: Learning and Memory: A Biological View. edited by Martinez, J. L. Jr. and Kesner, R. P., Academic Press, London, 1986, pp. 55-82.
Bliss, T. V. and Gardner-Medwin, A. R. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J. Physiol. 232, 357-374, 1973.
Bliss, T. V. and Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331-356, 1973.
Bliss, T. V. and Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31-39, 1993.
Bogoch, S. The Biochemistry of Memory. Oxford University Press, Oxford, 1968.
Brennan, F. E. and Fuller, P. J. Rapid upregulation of serum and glucocorticoid- regulated kinase (sgk) gene expression by corticosteroids in vivo. Mol. Cell Endocrinol. 166, 129-136, 2000.
Buse, P., Tran, S. H., Luther, E., Phu, P. T., Aponte, G. W. and Firestone G. L. Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum and glucocorticoid inducible protein kinase, Sgk, in mammary tumor cells: A novel convergence point of anti-proliferative and poroliferative cell signaling pathways. J. Biol. Chem. 274, 7253-7263, 1999.
Buzsaki, G. Long-term potentiation of the commissural path-CA1 pyramidal cell synapse in the hippocampus of the freely moving rat. Neurosci. Lett. 19, 293-296, 1980.
Casamayor, A., Torrance, P. D., Kobayashi, T., Thorner, J. and Alessi, D. R. Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. Curr. Biol. 9, 186-197, 1999.
Castelluci, V. F., Kennedy, T. E., Kandel, E. R. and Goelet, P. A quantitative analysis of 2-D gels identifies proteins in which labeling is increased following long-term sensitization in Aplysia. Neuron 1, 321-328, 1988.
Chang, H. P., Lindberg, F. P., Wang, H. L., Huang, A. M. and Lee, E. H. Y. Impaired memory retention and decreased long-term potentiation in integrin-associated protein-deficient mice. Learn. Mem. 6, 448-457, 1999.
Chen, S. Y., Bhargava, A., Mastroberardino, L., Meijer, O. C., Wang, J., Buse, P., Firestone, G. L., Verrey, F. and Pearce, D. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc. Natl. Acad. Sci. USA 96, 2514-2519, 1999.
Cintra, A., Zoli, M., Rosen, L., Agnati, L., Okret, S., Wikstrom, A. C., Gustafsson, J. Å. and Fuxe, K. Mapping and computer-assisted morphometry and microdensitometry of glucocorticoid immunoreactive neurons and glial cells in the rat central nervous system. Neuroscience 62, 843-897, 1994.
Cole, T. J., Blendy, J. A., Monaghan, A. P., Krieglstein, K., Schmid, W., Aguzzi, A., Fantuzzi, G., Hummler, E., Unsicker, K. and Schütz, G. Targeted disruption of the glucocorticoid receptor gene blocks adrenergic chromaffin cell development and severely retards lung maturation. Genes Dev. 9, 1608-1621, 1995.
Collingridge, G. L. and Bliss, T. V. P. Memories of NMDA receptors and LTP. Trends Neurosci. 18, 54-56, 1995.
Davis, H. P. and Squire, L. R. Protein synthesis and memory: a review. Psychol. Bull. 96, 518-559, 1984.
de Kloet, E. R., Vreugdenhil, E., Oitzl, M. S. and Joels, M. Brain corticosteroid receptor balance in health and disease. Endocr. Rev. 19, 269-301, 1998.
de Kloet, E. R., Oitzl, M. S. and Joels, M. Stress and cognition: are corticosteroids good or bad guys? Trends Neurosci. 22, 422-426, 1999.
Delmolino, L. M. and Castellot, J. J. Jr. Heparin suppresses sgk, an early response gene in proliferating vascular smooth muscle cells. J. Cell. Physiol. 173, 371-379, 1997.
Douglass, J., McKinzie, A. A. and Couceyro, P. PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J. Neurosci. 15, 2471-2481, 1995.
Drouin, J., Sun, Y. L., Chamberland, M., Gauthier, Y., de Lean, A., Nemer, M. and Schmidt, T. J. Novel glucocorticoid receptor complex with DNA element of the hormone-repressed POMC gene. EMBO J. 12, 145-156, 1993.
Dudai, Y. The Neurobiology of Memory: Concepts, Findings, Trends. Oxford University Press, New York, 1989.
Dunn, A. J. Biological correlates of learning and memory. in: Learning and Memory: A Biological View. edited by Martinez, J. L. Jr. and Kesner, R. P., Academic Press, London, 1986, pp. 165-201.
Eichenbaum, H., Stewart, C. and Morris, R. G. M. Hippocampal representation in place learning. J. Neurosci. 10, 3531-3542, 1990.
Fink, G. Mechanism of negative and positive feedback of steroids in the hypothalamic-pituitary system. in: Principles of Medical Biology. edited by Bittar, E. E. and Bittar, N., JAI Press, 1997, pp. 29-100.
Foster, T. C., Castro, C. A. and McNaughton, B. L. Spatial selectivity of rat hippocampal neurons: dependence on preparedness for movement. Science 244, 1580-1582, 1989.
Gottlieb, D. I. and Cowan, W. M. Autoradiographic studies of the commissural and ipsilateral association connection of the hippocampus and dentate gyrus of the rat. I. The commissural connections. J. Comp. Neurol. 149, 393-422, 1973.
Gould, E., Beylin, A., Tanapat, P., Reeves, A. and Shors, T. J. Learning enhances adult neurogenesis in the hippocampal formation. Nat. Neurosci. 2, 260-265, 1999.
Greenough, W. T. The possible role of experience-dependent synaptogenesis, or synapses on demand. in: Memory Systems of the brain. edited by Weinberger, N. M., McGaugh, J. L. and Lynch, G., Guilford Press, New York, 1985, pp. 77-106.
Greenough, W. T. and Chang, F. Synaptic structural correlates of information storage in mammalian nervous system. in: Synaptic Plasticity. edited by Cotman, C. W., Guilford Press, New York, 1985, pp. 335-372.
Guardiola-Diaz, H. M., Kolinske, J. S., Gates, L. H. and Seasholtz, A. F. Negative glucocorticoid regulation of cyclic adenosine 3’,5’-monophos- phate- stimulated corticotropin-releasing hormone-reporter expression in AtT-20 cells. Mol. Endocrinol. 10, 317-329, 1996.
Hebb, D. O. The Organization of Behavior. Wiley and Sons Inc., New York, 1949.
Hill, A. J. and Best, P. J. Effects of deafness and blindness on the spatial correlates of hippocampal unit activity in the rat. Exp. Neurol. 74, 204-217, 1981.
Hollenberg, S. M., Weinberger, C., Ong, E. S., Cerelli, G., Oro, A., Lebo, R., Thompson, E. B., Rosenfeld, M. G. and Evans, R. M. Primary structure and expression of a functional human glucocorticoid receptor cDNA. Nature 318, 635-641, 1985.
Hollister, R. D., Page, K. J. and Hyman, B. T. Distribution of the messenger RNA for the extracellularly regulated kinases 1,2 and 3 in rat brain: effects of excitotoxic hippocampal lesions. Neuroscience 79, 1111-1119, 1997.
Huang, A. M. and Lee, E. H. Y. Identification of a novel glial fibrillary acidic protein mRNA isotype related to memory retention in rats. Neuroreport 8, 1619-1624, 1997.
Huang, A. M., Wang, H. L., Tang, Y. P. and Lee, E. H. Y. Expression of integrin-associated protein gene associated with memory formation in rats. J. Neurosci. 18, 4305-4313, 1998.
Inokuchi, K., Kato, A., Hiraia, K., Hishinuma, F., Inoue, M. and Ozawa, F. Increase in activin beta A mRNA in rat hippocampus during long-term potentiation. FEBS Lett. 382, 48-52, 1996.
Imaizumi, K., Tsuda, M., Wanaka, A., Tohyama, M. and Takagi, T. Differential expression of sgk mRNA, a member of the Ser/Thr protein kinase gene family, in rat brain after CNS injury. Mol. Brain Res. 26, 189-196, 1994.
Isaacson, R. L. Experimental brain lesions and memory. in: Neuronal Mechanisms of Learning and Memory. edited by Rosenzweig, M. R. and Bennett, E. L., MIT Press, Cambridge, 1976, pp. 521-543.
Iyer, V. R., Eisen, M. B., Ross, D. T., Schuler, G., Moore, T., Lee, J. C. F., Trent, J. M., Staudt, L. M., Hudson, J. Jr., Boguski, M. S., Lashkari, D., Shalon, D., Botstein, D. and Brown, P. O. The transcriptional program in the response of human fibroblasts to serum. Science 283, 83-87, 1999.
Jansen, J. G., Vrieling, H., van Zeeland, A. A. and Mohn, G. R. The gene encoding hypoxanthine-guanine phosphoribosyltransferase as target for mutational analysis: PCR cloning and sequencing of the cDNA from the rat. Mutat. Res. 266, 105-116, 1992.
Jarrard, L. E. On the role of the hippocampus in learning and memory in the rat. Behav. Neural. Biol. 60, 9-26, 1993.
Jarrard, L. E. What does the hippocampus really do? Behav. Brain Res. 71, 1-10, 1995.
Kandel, E. R. Brain and behavior. in: Principles of Neuroal Science. edited by Kandel, E. R., Schwartz, J. H. and Jessell, T. M., Elsevier Science Publishing Co., New York, 1991, pp. 5-17.
Kim, J. J. and Yoon, K. S. Stress: metaplastic effects in the hippocampus. Trends Neurosci. 21, 505-509, 1998.
Kobayashi, T. and Cohen, P. Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. Biochem. J. 339, 319-328, 1999.
Kobayashi, T., Deak, M., Morrice, N. and Cohen, P. Characterization of the structure and regulation of two novel isoforms of serum- and glucocorticoid-induced protein kinase. Biochem. J. 344, 189-197, 1999.
Koda, L. H. and Bloom, F. E. A light and electron microscopic study of noradrenergic terminals in the rat dentate gyrus. Brain Res. 120, 325-335, 1957.
Kohler, C., Chan-Palay, V. and Wu, J. Y. Septal neurons containing glutamic acid decarboxylase immunoreactivity project to the hippocampal region in the rat brain. Anat. Embryol. (Berl.) 169, 41-44, 1984.
Konorski, J. Conditioned Reflexes and Neuron Organization. Cambridge University Press, Cambridge, 1948.
Korte, M., Griesbeck, O., Gravel, C., Carroll, P., Staiger, V., Thoenen, H. and Bonhoeffer, T. Virus-mediated gene transfer into hippocampal CA1 region restores long-term potentiation in brain-derived neurotrophic factor mutant mice. Proc. Natl. Acad. Sci. USA 93, 12547-12552, 1996.
Kumar, J. M., Brooks, D. P., Olson, B. A. and Laping, N. J. Sgk, a putative serine/threonine kinase, is differentially expressed in the kidney of diabetic mice and humans. J. Am. Soc. Nephrol. 10, 2488-2494, 1999.
Lee, E., Lein, E. S. and Firestone, G. L. Tissue-specific expression of the transcriptionally regulated serum and glucocorticoid-inducible protein kinase (Sgk) during mouse embryogenesis. Mech. Dev. 103, 177-181, 2001.
Lee, E. H. Y., Hung, H. C., Lu, K. T., Chen, W. H. and Chen, H. Y. Protein synthesis in the hippocampus associated with memory facilitation by corticotropin-releasing factor in rats. Peptides 13, 927-937, 1992.
Liang, P. and Pardee, A. B. Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967-971, 1992.
Liang, P., Averboukh, L. and Pardee, A. B. Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res. 21, 3269-3275, 1993.
Liu, W., Wang, J., Sauter, N. K. and Pearce, D. Steroid receptor heterodimerization demonstrated in vitro and in vivo. Proc. Natl. Acad. Sci. USA 92, 12480-12484, 1995.
Levy, W. B. and Steward, O. Temporal contiguity requirements for long-term associative potentiation/depression in the hippocampus. Neuroscience 8, 791-797, 1983.
Matthies, H. Biomedical, electrophysiological, and morphological corrected of brightness discrimination in rats. in: Brain Mechanisms in Memory and Learning: From the Single Neuron to Man. edited by Brazier, M. A. B., Raven Press, New York, 1979, pp. 197-215.
Matthies, H. Neurobiological aspects of learning and memory. Annu. Rev. Psychol. 40, 381-404, 1989.
Maiyar, A. C., Huang, A. J., Phu, P. T., Cha, H. H. and Firestone, G. L. p53 stimulates promoter activity of the sgk serum/glucocorticoid-inducible serine/threonine protein kinase gene in rodent mammary epithelial cells. J. Biol. Chem. 271, 12414-12422, 1996.
Maiyar, A. C., Phu, P. T., Huang, A. J. and Firestone, G. L. Repression of glucocorticoid receptor transactivation and DNA binding of a glucocorticoid response element within the serum/glucocorticoid-inducible protein kinase (sgk) gene promoter by the p53 tumor suppressor protein. Mol. Endocrinol. 11, 312-329, 1997.
McEwen, B. S., de Kloet, E. R. and Roste'ne, W. H. Adrenal steroid receptors and actions in the nervous system. Physiol. Rev. 66, 1121-1188, 1986.
McGaugh, J. L. and Herz, M. L. Memory Consolidation. Albion, San Francsico, 1972.
McNaughton, B. L., Douglas, R. M. and Goddard, G. V. Synaptic enhancement in fascia dentata: cooperativity among coactive afferents. Brain Res. 157, 277-293, 1978.
McNaughton, B. L., Barnes, C. A. and O’Keefe, J. The contribution of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp. Brain Res. 52, 41-49, 1983.
McNaughton, B. L., Barnes, C. A., Meltzer, J. and Sutherland, R. J. Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Exp. Brain Res. 76, 485-496, 1989.
Mikosz, C. A., Brickley, D. R., Sharkey, M. S., Moran, T. W. and Conzen, S. D. Glucocorticoid receptor-mediated protection from apoptosis is associated with induction of the serine/threonine survival kinase gene, sgk-1. J. Biol. Chem. 276, 16649-16654, 2001.
Miller, W. L. and Blake Tyrrel, J. The adrenal cortex. in: Endocrinology and Metabolism. edited by Felig, P., Baxter, J. D. and Frohman, L. A., McGraw-Hill, New York, 1995, pp. 555-711.
Mizuno, H. and Nishida, E. The ERK MAP kinase pathway mediates induction of SGK (serum- and glucocorticoid-inducible kinase) by growth factors. Genes Cells 6, 261-268, 2001.
Moore, R. Y. and Halaris, A. E. Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat. J. Comp. Neurol. 164, 171-183, 1975.
Morimoto, M., Morita, N., Ozawa, H., Yokoyama, K. and Kawata, M. Distribution of glucocorticoid receptor immunoreactivity and mRNA in the rat brain: an immunohistochemical and in situ hybridization study. Neurosci. Res. 26, 235-269, 1996.
Morris, R. G. M., Garrud, P., Rawlins, J. N. P. and O’Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681-683, 1982.
Morris, R. G. M. Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47-60, 1984.
Morris, R. G. M., Halliwell, R. F. and Bowery, N. Synaptic plasticity and learning. II: Do different kinds of plasticity underlie different kinds of learning? Neuropsychologia. 27, 41-59, 1989.
Moser, E., Moser, M. B. and Andersen, P. Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions. J. Neurosci. 13, 3916-3925, 1993.
Moser, M. B., Moser, E. I., Forrest, E., Andersen, P. and Morris, R.G.M. Spatial learning with a minislab in the dorsal hippocampus. Proc. Natl. Acad. Sci. USA 92, 9697-9701, 1995.
Moser, M. B. and Moser, E. I. Pretraining and the function of hippocampal long-term potentiation. Neuron 26, 559-561, 2000.
Naray-Fejes-Toth, A., Canessa, C., Cleaveland, E. S., Aldrich, G. and Fejes-Toth, G. Sgk is an aldosterone-induced kinase in the renal collecting duct. J. Biol. Chem. 274, 16973-16978, 1999.
Naray-Fejes-Toth, A. and Fejes-Toth, G. The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel. Kidney Inter. 57, 1290-1294, 2000.
Naray-Fejes-Toth, A., Fejes-Toth, G., Volk, K. A. and Stokes, J. B. SGK is a primary glucocorticoid-induced gene in the human. J. Steroid Biochem. Mol. Biol. 75, 51-56, 2000.
Oitzl, M. S. and de Kloet, E. R. Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning. Behav. Neurosci. 108, 62-71, 1992.
Oitzl, M. S., de Kloet, E. R., Joels, M., Schmid, W. and Cole, T. J. Spatial learning deficits in mice with a targeted glucocorticoid receptor gene disruption. Eur. J. Neurosci. 9, 2284-2296, 1997.
Oitzl, M. S., Fluttert, M., Sutanto, W. and de Kloet, E. R. Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats. Eur. J. Neurosci. 10, 3759-3766, 1998.
Oitzl, M. S., Reichardt, H. M., Joels, M. and de Kloet, E. R. Point mutation in the mouse glucocorticoid receptor preventing DNA binding impairs spatial memory. Proc. Natl. Acad. Sci. USA 98, 12790-12795, 2001.
O’Keefe, J. and Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171-175, 1971.
Olton, D. S., Walker, J. A. and Gage, F. H. Hippocampal connections and spatial discrimination. Brain Res. 139, 295-308, 1978.
Olton, D. S., Branch, M. and Best, P. J. Spatial correlates of hippocampal unit activity. Exp. Neurol. 58, 387-409, 1978.
Park, J., Leong, M. L., Buse, P., Maiyer, A. C., Firestine, G. L. and Hemmings, B. A. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 18, 3024-3033, 1999.
Patel, S. N. and Stewart, M. G. Changes in the number and structure of dendritic spines 25 hours after passive avoidance training in the domestic chick, Gallus domesticus. Brain Res. 449, 34-46, 1988.
Pavlides, C., Ogawa, S., Kimura, A. and McEwen, B. S. Role of adrenal steroid mineralcorticoid and glucocorticoid receptors in long-term potentiation in the CA1 field of hippocampal slices. Brain Res. 738, 229-235, 1996.
Pearce, D., Verrey, F., Chen, S. Y., Mastroberardino, L., Meijer, O. C., Wang, J. and Bhargava, A. Role of SGK in mineralocorticoid-regulated sodium transport. Kidney Inter. 57, 1283-1289, 2000.
Perrotti, N., He, R. A., Phillips, S. A., Haft, C. R. and Taylor, S. I. Activation of serum- and glucocorticoid-induced protein kinase (Sgk) by cyclic AMP and insulin. J. Biol. Chem. 276, 9406-9412, 2001.
Pfahl, M. Nuclear receptor/AP-1 interaction. Endocr. Rev. 14, 651-658, 1993.
Popov, N., Schulzeck, S., Pohle, W. and Matthies, H. Changes in the incorporation of [3H] fucose into rat hippocampus after acquisition of a brightness discrimination reaction. An electrophoretic study. Neuroscience 5, 161-167, 1980.
Ray, A. and Prefontaine, K. E. Physical association and functional antagonism between the p65 subunit of transcription factor NFkappaB and the glucocorticoid receptor. Proc. Natl. Acad. Sci. USA 91, 752-756, 1994.
Rehkamper, G., Haase, E. and Frahm, H. D. Allometric comparison of brain weight and brain structure volumes in different breeds of the domestic pigeon, Columba livia f.d. (fantails, homing pigeons, strassers). Brain Behav. Evol. 31, 141-149, 1988.
Reul, J. M. H. M. and de Kloet, E. R. Two receptor systems for corticosterone in rat brain: microdissection and differential occupation. Endocrinology 117, 2505-2512, 1985.
Reul, J. M. H. M. and de Kloet, E. R. Anatomical resolution of two types of corticosterone receptor sites in rat brain with in vivo autoradiography and computerized image analysis. J. Steroid Biochem. 24, 269-272, 1986.
Reul, J. M. H. M., de Kloet, E. R., Van Sluijs, F. J., Rijnberk, A. and Rothuizen, J. Binding characteristics of mineralocorticoid and glucocorticoid receptors in dog brain and pituitary. Endocrinology 127, 907-915, 1990.
Roozendaal, B., Portillo-marquez, G. and McGaugh, J. L. Basolateral amygdala lesions block glucocorticoid-induced modulation of memory for spatial learning. Behav. Neurosci. 110, 1074-1083, 1996.
Roozendaal, B. Glucocorticoids and the regulation of memory consolidation. Psychoneuroendocrinology 25, 213-238, 2000.
Rosenzweig, M. R. and Bennett, E. L. Experimental brain lesions and memory. in: Neuronal Mechanisms of Learning and Memory. edited by Rosenzweig, M. R. and Bennett, E. L., MIT Press, Cambridge, 1976.
Rousse, I., Beaulieu, S., Rowe, W., Meaney, M. J., Barden, N. and Rochford, J. Spatial memory in transgenic mice with impaired glucocorticoid receptor function. Neuroreport 8, 841-845, 1997.
Rutledge, L. T. Synaptogenesis: Effects of synaptic use. in: Neuronal Mechanism of Learning and Memory. edited by Rosenzweig, M. R. and Bennett, E. L., MIT Press, Cambridge, 1976, pp. 329-339.
Sandi, C. The role and mechanisms of action of glucocorticoid involvement in memory storage. Neural Plast. 6, 41-52, 1998.
Schenk, F. and Morris, R. G. M. Dissociation between components of spatial memory in rats after recovery from the effects of retrohippocampal lesions. Exp. Brain Res. 58, 11-28, 1985.
Schmitz, D., Schuchmann, S., Fisahn, A., Draguhn, A., Buhl, E. H., Petrasch-Parwez, E., Dermietzel, R., Heinemann, U. and Traub, R. D. Axo-axonal coupling. a novel mechanism for ultrafast neuronal communication. Neuron 31, 831-840, 2001.
Segal, M. Physiological and pharmacological evidence for a serotonergic projection to the hippocampus. Brain Res. 94, 115-131, 1975.
Shepherd, G. M. and Koch, C. Introduction to synaptic circuits. in: The Synaptic Organization of the brain. edited by Shepherd, G. M., Oxford Press, New York, 1988, pp. 3-31.
Sherry, D. F., Vaccarino, A. L., Buckenham, K. and Herz, R. S. The hippocampal complex of food-storing birds. Brain Behav. Evol. 34, 308-317, 1989.
Squire, L. R., Slater, P. C. and Chace, P. M. Retrograde amnesia: temporal gradient in very long term memory following electroconvulsive therapy. Science 187, 77-79, 1975.
Squire, L. R. Memory and Brain. Oxford University Press, New York, 1987.
Squire, L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195-231, 1992.
Squire, L. R. and Alvarez, P. Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr. Opin. Neurobiol. 5, 169-177, 1995.
Sutherland, R. J., Whishaw, I. Q. and Kolb, B. A behavioural analysis of spatial localization following electrolytic, kainate- or colchicine-induced damage to the hippocampal formation in the rat. Behav. Brain Res. 7, 133-153, 1983.
Swanson, L. W. and Hartman, B. K. The central adrenergic system. An immunofluorescence study of the location of cell bodies and their efferent connections in the rat utilizing dopamine-beta-hydroxylase as a marker. J. Comp. Neurol. 163, 467-505, 1975.
Taube, J. S., Muller, R. U. and Ranck, J. B. Jr. Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis. J. Neurosci. 10, 420-435, 1990.
Taube, J. S., Muller, R. U. and Ranck, J. B. Jr. Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations. J. Neurosci. 10, 436-447, 1990.
Taube, J. S., Kesslak, J. P. and Cotman, C. W. Lesions of the rat postsubiculum impair performance on spatial tasks. Behav. Neural Biol. 57, 131-143, 1992.
Thompson, R. F. and Donegan, N. H. The search for the engram. in: Learning and Memory: A Biological View. edited by Martinez, J. L. Jr. and Kesner, R. P., Academic Press, London,1986, pp. 3-52.
Trapp, T., Rupprecht, R., Castre'n, M., Reul, J. M. H. M. and Holsboer, F. Heterodimerization between mineralocorticoid and glucocorticoid receptor: a new principle of glucocorticoid action in the CNS. Neuron 13, 1457-1462, 1994.
Traub, R. D. and Bibbig, A. A model of high-frequency ripples in the hippocampus based on synaptic coupling plus axon-axon gap junctions between pyramidal neurons. J. Neurosci. 20, 2086-2093, 2000.
Tully, T. Discovery of genes involved with learning and memory: an experimental synthesis of Hirschian and Benzerian perspectives. Proc. Natl. Acad. Sci. USA 93, 13460-13467, 1996.
van Steensel, B., van Binnendijk, E. P., Hornsby, C. D., van der Voort, H. T., Krozowski, Z. S., de Kloet, E. R. and van Driel, R. Partial colocalization of glucocorticoid and mineralocorticoid receptors in discrete nuclear domains. J. Cell Sci. 109, 787-792, 1996.
Wagner, C. A., Broer, A., Albers, A., Gamper, N., Lang, F. and Broer, S. The heterodimeric amino acid transporter 4F2hc/LAT1 is associated in Xenopus oocytes with a non-selective cation channel that is regulated by the serine/threonine kinase sgk-1. J. Physiol. (Lond.) 526, 35-46, 2000.
Waldegger, S., Barth, P., Raber, G., and Lang, F. Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc. Natl. Acad. Sci. USA 94, 4440-4445, 1997.
Waldegger, S., Klingel, K., Barth, P., Sauter, M., Rfer, M. L., Kandolf, R. and Lang, F. h-sgk serine-threonine protein kinase gene as transcriptional target of transforming growth factor beta in human intestine. Gastroenterology 116, 1081-1088, 1999.
Webster, M. K., Goya, L. and Firestone, G. L. Immediate-early transcriptional regulation and rapid mRNA turnover of a putative serine/threonine protein kinase. J. Biol. Chem. 268, 11482-11485, 1993.
Webster, M. K., Goya, L., Ge, Y., Maiyar, A. C. and Firestone, G. L. Characterization of sgk, a novel member of the serine/threonine protein kinase gene family which is transcriptionally induced by glucocorticoids and serum. Mol. Cell. Biol. 13, 2031-2040, 1993.
Zilliacus, J., Wright, A. P. H., Carlstedt-Duke, J. and Gustafsson, J. Å. Structural determinants of DNA-binding specificity by steroid receptors. Mol. Endocrinol. 9, 389-400, 1995.
Zola-Morgan, S., Squire, L. R. and Amaral, D. G. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J. Neurosci. 6, 2950-2967, 1986.