Rescuing impairment of long-term potentiation in fyn-deficient mice by introducing Fyn transgene

• DOI: 10.1073/pnas.94.9.4761
• Publication Date: 2002-07-26T14:35:50Z
• Authors: Nobuhiko Kojima; Jian Wang; Isabelle M. Mansuy; Seth G. N. Grant; Mark Mayford; Eric R. Kandel
• Keywords: Neurons; 0303 health sciences; Long-Term Potentiation; Proto-Oncogene Proteins pp60(c-src); Age Factors; Mice, Transgenic; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-fyn; Hippocampus; Mice; 03 medical and health sciences; Proto-Oncogene Proteins; Animals

To examine the physiological role of the Fyn tyrosine kinase in neurons, we generated transgenic mice that expressed a fyn cDNA under the control of the calcium/calmodulin-dependent protein kinase IIα promoter. With this promoter, we detected only low expression of Fyn in the neonatal brain. In contrast, there was strong expression of the fyn-transgene in neurons of the adult forebrain. To determine whether the impairment of long-term potentiation (LTP) observed in adult fyn-deficient mice was caused directly by the lack of Fyn in adult hippocampal neurons or indirectly by an impairment in neuronal development, we generated fyn-rescue mice by introducing the wild-type fyn-transgene into mice carrying a targeted deletion in the endogenous fyn gene. In fyn-rescue mice, Schaffer collateral LTP was restored, even though the morphological abnormalities characteristic of fyn-deficient mice were still present. These results suggest that Fyn contributes, at least in part, to the molecular mechanisms of LTP induction.