Impaired Long-Term Potentiation, Spatial Learning, and Hippocampal Development in fyn Mutant Mice

• Published in: Science (American Association for the Advancement of Science) Vol. 258; no. 5090; pp. 1903 - 1910
• Main Authors: Seth G. N. Grant, O'Dell, Thomas J., Karl, Kevin A., Stein, Paul L., Soriano, Philippe, Kandel, Eric R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 18.12.1992; American Association for the Advancement of Science
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Acetylcholinesterase - analysis; Animals; Biological and medical sciences; Brain - cytology; Brain - physiology; Central nervous system; Cerebral Cortex - cytology; Cerebral Cortex - physiology; Developmental neurophysiology; Electric Stimulation; Electrophysiology; Fundamental and applied biological sciences. Psychology; Genes, abl; Genes, src; Genetic mutation; Hippocampus; Hippocampus (Brain); Hippocampus - drug effects; Hippocampus - growth & development; Hippocampus - physiology; In Vitro Techniques; Learning; Long term potentiation; Mice; Mice, Neurologic Mutants; N methyl D aspartate receptors; Neurons; Neurons - drug effects; Neurons - physiology; Physiological aspects; Protein tyrosine kinase; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-fyn; Proto-Oncogene Proteins c-yes; Pyramidal cells; Pyramidal Tracts - physiology; Receptors; Receptors, N-Methyl-D-Aspartate - physiology; Space Perception; src-Family Kinases; Synapses - physiology; T lymphocytes; Tetanus; Vertebrates: nervous system and sense organs; Potentiation; Rodentia; Central nervous system; Electrophysiology; Long term; Learning; Vertebrata; Mammalia; Acquisition process; Mouse; Development; Excitatory postsynaptic potential; Hippocampus; Brain (vertebrata)
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1361685

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.