RESCUING IMPAIRMENT OF LONG-TERM POTENTIATION IN FYN-DEFICIENT MICE BY INTRODUCING FYN TRANSGENE

To examine the physiological role of the Fyn tyrosine kinase in neuron s, we generated transgenic mice that expressed a fyn cDNA under the co ntrol of the calcium/calmodulin-dependent protein kinase II alpha prom oter, With this promoter, we detected only low expression of Fyn in th e 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-defic ient mice was caused directly by the lack of Fyn in adult hippocampal neurons or indirectly by an impairment in neuronal development, we gen erated 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 mor phological abnormalities characteristic of fyn-deficient mice were sti ll present, These results suggest that Fyn contributes, at least in pa rt, to the molecular mechanisms of LTP induction.