Journal of Molecular Neuroscience

, Volume 17, Issue 3, pp 397–404 | Cite as

Identification of maze learning-associated genes in rat hippocampus by cDNA microarray

  • Yongquan Luo
  • Jeffrey M. Long
  • Edward L. Spangler
  • Dan L. Longo
  • Donald K. Ingram
  • Nan-ping Weng


Long-term memory formation requires de novo RNA and protein synthesis. To assess gene-expression changes associated with learning and memory processes, we used cDNA microarray to analyze hippocampal gene expression in male Fischer-344 rats following training in a multiunit T-maze. Here, we report the identification of 28 clones (18 known genes and 10 ESTs) for which expression increased after the maze learning. Some of the known genes appear to be involved in Ca2+ signaling, Ras activation, kinase cascades, and extracellular matrix (ECM) function, which may regulate neural transmission, synaptic plasticity, and neurogenesis. The geneexpression profile presented here provides the groundwork for future, more focused research to elucidate the contribution of these genes in learning and memory processes.

Index Entries

Memory RT-PCR neuronal growth neuronal remodeling singal transduction gene expression 


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  1. Agassandian C., Plantier M., Fattoum A., Represa A., and der Terrossian E. (2000) Subcellular distribution of calponin and caldesmon in rat hippocampus. Brain Res. 887, 444–449.PubMedCrossRefGoogle Scholar
  2. Bajetto A., Bonavia R., Barbero S., Piccioli P., Costa A., Florio T., and Schettini G. (1999) Glial and neuronal cells express functional chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor 1. J. Neurochem. 73, 2348–2357.PubMedCrossRefGoogle Scholar
  3. Carlisle A. J., Prabhu V. V., Elkahloun A., Hudson J., Trent J. M., Linehan W. M., et al. (2000) Development of a prostate cDNA microarray and statistical gene expression analysis package. Mol. Carcinog. 28, 12–22.PubMedCrossRefGoogle Scholar
  4. Chang H. P., Lindberg F. P., Wang H. L., Huang A. M., and Lee E. H. (1999) Impaired memory retention and decreased long-term potentiation in integrin-associated protein-deficient mice. Learn Mem. 6, 448–457.PubMedCrossRefGoogle Scholar
  5. Colucci-Guyon E., Gimenez Y., Ribotta M., Maurice T., Babinet C., and Privat A. (1999) Cerebellar defect and impaired motor coordination in mice lacking vimentin. Glia 25, 33–43.PubMedCrossRefGoogle Scholar
  6. Davis H. P. and Squire L. R. (1984) Protein synthesis and memory: a review. Psychol. Bull. 96, 518–559.PubMedCrossRefGoogle Scholar
  7. Gurney M. E., Heinrich S. P., Lee M. R., and Yin H.-S. (1986) Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science 234, 566–574.PubMedCrossRefGoogle Scholar
  8. Hagler D. J. J. and Goda Y. (1998) Synaptic adhesion: the building blocks of memory? Neuron 20, 1059–1062.PubMedCrossRefGoogle Scholar
  9. Huang A. M., Wang H. L., Tang Y. P., and Lee E. H. (1998) Expression of integrin-associated protein gene associated with memory formation in rats. J. Neurosci. 18, 4305–4313.PubMedGoogle Scholar
  10. Impey S., Obrietan K., and Storm D. R. (1999) Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity. Neuron 23, 11–14.PubMedCrossRefGoogle Scholar
  11. Ingram D. K., Shimada A., Spangler E. L., Ikari H., Hengemihle J., Kuo H., and Greig N. (1996) Congnitive enhance cement: new strategies for stimulatng cholinergic, glutamatergic, and nitric oxide systems. Ann. NY Acad. Sci. 786, 348–361.PubMedCrossRefGoogle Scholar
  12. Jadayel D. M., Osborne L. R., Coignet L. J. A., Zani V. J., Tsui L. C., Scherer S. W., and Dyer M. J. (1998) The BCL7 gene family: deletion of BCL7B in Williams syndrome. Gene 224, 35–44.PubMedCrossRefGoogle Scholar
  13. Jin L., Thompson C. A., Qian X., Kuecker S. J., Kulig E., and Lloyd R. V. (1999) Analysis of anterior pituitary hormone mRNA expression in immunophenotypically characterized single cells after laser capture microdissection. Lab. Invest. 79, 511–512.PubMedGoogle Scholar
  14. Kadmon G., von Bohlen und Halbach F., Horstkorte R., Eckert M., Altevogt P., and Schachner M. (1995) Evidence for cis in teraction and cooperative signalling by the heat-stable antigen nectadrin (murine CD24) and the cell adhesion molecule L1 in neurons. Eur. J. Neurosci. 7, 993–1004.PubMedCrossRefGoogle Scholar
  15. Kumar V. B., Franko M. W., Farr S. A., Armbrecht H. J., and Morley J. E. (2000) Identification of agedependent changes in expression of senescence-accelerated mouse (SAMP8) hippocampal proteins by expression array analysis. Biochem. Biophys. Res. Commun. 272, 657–661.PubMedCrossRefGoogle Scholar
  16. Lee C.-K., Klopp R. G., Weindruch R., and Prolla T. A. (1999) Gene expression profile of aging and its retardation by caloric restriction. Science 285, 1390–1393.PubMedCrossRefGoogle Scholar
  17. Lee C. K., Weindruch R., and Prolla T. A. (2000a) Geneexpression profile of the ageing brain in mice. Nat. Genet. 294–297.Google Scholar
  18. Lee E. H., Hsieh Y. P., Yang C. L., Tsai K. J., and Liu C. H. (2000b) Induction of integrin-associated protein (IAP) mRNA expression during memory consolidation in rat hippocampus. Eur. J. Neurosci. 12, 1105–1112.PubMedCrossRefGoogle Scholar
  19. Lee M. R., Ho D. D., and Gurney M. E. (1987) Functional interaction and partial homology between human immunodeficiency virus and neuroleukin. Science 237, 1047–1051.PubMedCrossRefGoogle Scholar
  20. Leon J., Guerrero I., and Pellicer A. (1987) Differential expression of the ras gene family in mice. Mol. Cell. Biol. 7, 1535–1540.PubMedGoogle Scholar
  21. Ly D. H., Lockhart D. J., Lerner R. A., and Schultz P. G. (2000) Mitotic misregulation and human aging. Science 287, 2486–2492.PubMedCrossRefGoogle Scholar
  22. Mayford M. and Kandel E. R. (1999) Genetic approaches to memory storage. Trends Genet. 15, 463–470.PubMedCrossRefGoogle Scholar
  23. Mazzucchelli C. and Brambilla R. (2000) Ras-related and MAPK signalling in neuronal plasticity and memory formation. Cell. Mol. Life Sci. 57, 604–611.PubMedCrossRefGoogle Scholar
  24. Miyamoto S., Teramoto H., Coso O., Gutkind J., Burbelo P., Akiyama S., and Yamada K. (1995) Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. J. Cell Biol. 131, 791–805.PubMedCrossRefGoogle Scholar
  25. Murase S. and Schuman E. M. (1999) The role of cell adhesion molecules in synaptic plasticity and memory. Curr. Opin. Cell. Biol. 11, 549–553.PubMedCrossRefGoogle Scholar
  26. Nakamura T., Sanokawa R., Sasaki Y. F., Ayusawa D., Oishi M., and Mori N. (1995) Cyclin I: a new cyclin encoded by a gene isolated from human brain. Exp. Cell. Res. 221, 534–542.PubMedCrossRefGoogle Scholar
  27. Platenik J., Kuramoto N., and Yoneda Y. (2000) Molecular mechanisms associated with long-term consolidation of the NMDA signals. Life Sci. 67, 335–364.PubMedCrossRefGoogle Scholar
  28. Rampon C., Jiang C. H., Dong H., Tang Y. P., Lockhart D. J., Schultz P. G., et al. (2000) Effects of environmental enrichment on gene expression in the brain. Proc. Natl. Acad. Sci. USA 97, 12,880–12,884.CrossRefGoogle Scholar
  29. Saatman K. E., Contreras P. C., Smith D. H., Raghupathi R., McDermott K. L., Fernandez S. C., et al. (1997) Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp. Neurol. 147, 418–427.PubMedCrossRefGoogle Scholar
  30. Schena M., Heller R. A., Theriault T. P., Konrad K., Lachenmeier E., and Davis R. W. (1998) Microarrays: biotechnology’s discovery platform for functional genomics. Trends Biotechnol. 16, 301–306.PubMedCrossRefGoogle Scholar
  31. Uetani N., Kato K., Ogura H., Mizuno K., Kawano K., Mikoshiba K., et al. (2000) Impaired learning with enhanced hippocampal long-term potentiation in PTPdelta-deficient mice. EMBO J. 19, 2775–2785.PubMedCrossRefGoogle Scholar
  32. Watanabe H., Carmi P., Hogan V., Raz T., Silletti S., Nabi I. R., and Raz A. (1991) Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor. J. Biol. Chem. 266, 13,442–13,448.Google Scholar
  33. Yun H. Y., Dawson V. L., and Dawson T. M. (1999) Glutamate-stimulated calcium activation of Ras/Erk pathway mediated by nitric oxide. Diabetes. Res. Clin. Pract. 45, 113–115.PubMedCrossRefGoogle Scholar
  34. Zani V. J., Asou N., Jadayel D., Heward J. M., Shipley J., Nacheva E., et al. (1996) Molecular cloning of complex chromosomal translocation t(8;14;12)(q24.1;q32 3;q24.1) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon. Blood 87, 3124–3134.PubMedGoogle Scholar
  35. Zhao W., Chen H., Xu H., Moore E., Meiri N., Quon M. J., and Alkon D. L. (1999) Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J. Biol. Chem. 274, 34,893–34,902.Google Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  • Yongquan Luo
    • 1
  • Jeffrey M. Long
    • 2
  • Edward L. Spangler
    • 2
  • Dan L. Longo
    • 1
  • Donald K. Ingram
    • 2
  • Nan-ping Weng
    • 1
  1. 1.Laboratory of ImmunologyNational Institute on Aging, National Institutes of HealthBaltimore
  2. 2.Laboratory of NeurosciencesNational Institute on Aging, National Institutes of HealthBaltimore

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