FYN TYROSINE KINASE IS REQUIRED FOR NORMAL AMYGDALA KINDLING

To identify specific genes involved with epileptogenesis kindling was examined in mice carrying mutations engineered by gene targeting. Amyg dala kindling was tested in mice with a null-mutation in the Fyn tyros ine kinase gene, a mutation that raises the threshold for the inductio n of long-term potentiation in the hippocampus. The fyn mutants had a normal threshold, duration and stability of epileptiform after-dischar ge, which is crucial for kindling. Despite the normal after-discharge, fyn mutants showed a striking retardation in the rate of kindling. On ce the kindled state was established in fyn mutants it remained stable . This implicates a Fyn-dependent biochemical pathway in the induction but not the maintenance of normal amygdala kindling. fyn is the first gene identified to be required for normal epileptogenesis.