Altered hippocampal network excitability in the hypernoradrenergic mutant mouse tottering.

A latent, gene-linked alteration of hippocampal network excitability in tg/tg mutant mice was unmasked in vitro by convulsant-activated synchronous neuronal discharges. Exposure to elevated extracellular potassium ions or 4-aminopyridine, but not picrotoxin, revealed an abnormally prolonged network discharge duration in the mutant CA3 pyramidal cell region. In both phenotypes, noradrenaline, and a selective beta-noradrenergic receptor agonist, isoproterenol, reversibly accelerated the frequency of the discharges. These findings identify an intrinsic alteration in the excitability of an isolated neuronal network in a model of inherited generalized spike-wave epilepsy, and further implicate noradrenergic mechanisms in the temporal modulation of hippocampal synchronization and epileptogenesis.