Fyn tyrosine kinase is required for normal amygdala kindling

Cain, Donald P.; Grant, Seth G.N.; Saucier, Deborah; Hargreaves, Eric L.; Kandel, Eric R.

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Volume 22, Issue 2 , Pages 107-114, October 1995

Fyn tyrosine kinase is required for normal amygdala kindling

Donald P. Cain
- Corresponding author.
- Department of Psychology, Graduate Program in Neuroscience, University of Western Ontario, London, Ontario N6A 5C2, Canada
Seth G.N. Grant
- Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University New York, NY 10032, USA
- Center for Genome Research, The University of Edinburgh, King's Buildings, West Main Road, Edinburgh EH9 3JQ, United Kingdom
Deborah Saucier
- Department of Psychology, Graduate Program in Neuroscience, University of Western Ontario, London, Ontario N6A 5C2, Canada
Eric L. Hargreaves
- Department of Psychology, Graduate Program in Neuroscience, University of Western Ontario, London, Ontario N6A 5C2, Canada
- Department of Psychology, McGill University, Montreal, Quebec H3A 1B1, Canada
Eric R. Kandel
- Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University New York, NY 10032, USA
- Howard Hughes Medical Institute, 722 West 168th Street, New York, NY 10032, USA

Received 14 September 1994; accepted 3 April 1995.

Abstract

To identify specific genes involved with epileptogenesis kindling was examined in mice carrying mutations engineered by gene targeting. Amygdala kindling was tested in mice with a null-mutation in the Fyn tyrosine kinase gene, a mutation that raises the threshold for the induction of long-term potentiation in the hippocampus. The fyn mutants had a normal threshold, duration and stability of epileptiform after-discharge, which is crucial for kindling. Despite the normal after-discharge, fyn mutants showed a striking retardation in the rate of kindling. Once 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.

Keywords: Gene targeting, Epileptogenesis

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