Abnormal synaptic transmission in the olfactory bulb of Fyn-kinase-deficient mice.
We studied synaptic transmission in the granule cells in the olfactory bulb of the homozygous Fyn (a nonreceptor type tyrosine kinase)-deficient (fynz/fynz) and heterozygous Fyn-deficient (+/fynz) mice by using slice preparations from the olfactory bulb. Stimulation to the lateral olfactory tract and/or centrifugal fibers to the olfactory bulb evoked field excitatory postsynaptic potentials (fEPSPs) in the granule cells. In +/fynz mice, fEPSPs were augmented by bicuculline, a gamma-aminobutyric acid (GABAA) antagonist and picrotoxin, whereas fEPSPs in fynz/fynz mice were much less sensitive to bicuculline and picrotoxin. Application of D-2-amino-5-phosphonopentanoic acid had no effect but 6-cyano-7-nitroquinoxaline-2,3-dione produced almost complete block of fEPSPs in both +/fynz mice and fynz/fynz mice. (1S,3R)-1-aminocyclo-pentane-1.3-dicarboxylate, an agonist of metabotropic glutamate receptors caused a similar depression of fEPSPs in both +/fynz and fynz/fynz mice. In +/fynz mice tetanic stimulation to the lateral olfactory tract and/or centrifugal fibers induced N-methyl-D-aspartate (NMDA)-dependent long-term potentiation (LTP) of fEPSPs, whereas LTP was impaired in fynz/fynz mice. Our results demonstrate altered functions of GABAA and NMDA receptors in the olfactory system of Fyn-deficient mice.
Kitazawa
H
H
Department of Physiology, Jichi Medical School, Tochigi 329-04, Japan.
Yagi
T
T
Miyakawa
T
T
Niki
H
H
Kawai
N
N
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003433:Crosses, Genetic; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists; D006579:Heterozygote; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D017470:Receptors, Glutamate / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D003515:Cycloleucine; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D018696:Neuroprotective Agents; D010852:Picrotoxin; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051076:Proto-Oncogene Proteins c-fyn; D017470:Receptors, Glutamate; C036361:1-amino-1,3-dicarboxycyclopentane; C494960:Fyn protein, mouse