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Science 18 December 1992:
Vol. 258. no. 5090, pp. 1903 - 1910
DOI: 10.1126/science.1361685
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Articles

Science, Vol 258, Issue 5090, 1903-1910
Copyright © 1992 by American Association for the Advancement of Science

articles

Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice

SG Grant, TJ O'Dell, KA Karl, PL Stein, P Soriano, and ER Kandel

Center for Neurobiology and Behavior, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and abl, were used to study the role of these kinases in long-term potentiation (LTP) and in the relation of LTP to spatial learning and memory. All four kinases were expressed in the hippocampus. Mutations in src, yes, and abl did not interfere with either the induction or the maintenance of LTP. However, in fyn mutants, LTP was blunted even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation, were normal. In parallel with the blunting of LTP, fyn mutants showed impaired spatial learning, consistent with a functional link between LTP and learning. Although fyn is expressed at mature synapses, its lack of expression during development resulted in an increased number of granule cells in the dentate gyrus and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.


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PNAS 96, 2461-2466
   Abstract »    Full Text »    PDF »
The Glutamate Receptor Ion Channels.
R. Dingledine, K. Borges, D. Bowie, and S. F. Traynelis (1999)
Pharmacol. Rev. 51, 7-62
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Reg1ulatory Role and Molecular Interactions of a Cell-Surface Heparan Sulfate Proteoglycan (N-syndecan) in Hippocampal Long-Term Potentiation.
S. E. Lauri, S. Kaukinen, T. Kinnunen, A. Ylinen, S. Imai, K. Kaila, T. Taira, and H. Rauvala (1999)
J. Neurosci. 19, 1226-1235
   Abstract »    Full Text »    PDF »
The fyn art of N-methyl-D-aspartate receptor phosphorylation.
C. Sala and M. Sheng (1999)
PNAS 96, 335-337
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PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A.
T. Tezuka, H. Umemori, T. Akiyama, S. Nakanishi, and T. Yamamoto (1999)
PNAS 96, 435-440
   Abstract »    Full Text »    PDF »
Src-Related Protein Tyrosine Kinases in Hematopoiesis.
S. J. Corey and S. M. Anderson (1999)
Blood 93, 1-14
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Higher Seizure Susceptibility and Enhanced Tyrosine Phosphorylation of N-Methyl-D-Aspartate Receptor Subunit 2B in fyn Transgenic Mice.
N. Kojima, H. Ishibashi, K. Obata, and E. R. Kandel (1998)
Learn. Mem. 5, 429-445
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Enhanced Hippocampal CA1 LTP but Normal Spatial Learning in Inositol 1,4,5-trisphosphate 3-kinase(A)-Deficient Mice.
K. Jun, G. Choi, S.-G. Yang, K. Y. Choi, H. Kim, G. C.K. Chan, D. R. Storm, C. Albert, G. W. Mayr, C.-J. Lee, et al. (1998)
Learn. Mem. 5, 317-330
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Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT/enhancer binding protein delta.
E. Sterneck, R. Paylor, V. Jackson-Lewis, M. Libbey, S. Przedborski, L. Tessarollo, J. N. Crawley, and P. F. Johnson (1998)
PNAS 95, 10908-10913
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Protein Kinases, Protein Phosphorylation, and the Regulation of Insulin Secretion from Pancreatic {beta}-Cells..
P. M. Jones and S. J. Persaud (1998)
Endocr. Rev. 19, 429-461
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Common in Vitro Substrate Specificity and Differential Src Homology 2 Domain Accessibility Displayed by Two Members of the Src Family of Protein-tyrosine Kinases, c-Src and Hck.
R. J. Sicilia, M. L. Hibbs, P. A. Bello, J. D. Bjorge, D. J. Fujita, I. J. Stanley, A. R. Dunn, and H.-C. Cheng (1998)
J. Biol. Chem. 273, 16756-16763
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Dynamic characteristics and adaptability of mouse vestibulo-ocular and optokinetic response eye movements and the role of the flocculo-olivary system revealed by chemical lesions.
A. Katoh, H. Kitazawa, S. Itohara, and S. Nagao (1998)
PNAS 95, 7705-7710
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