Persistently modified h-channels after complex febrile seizures convert the seizure-induced enhancement of inhibition to hyperexcitability

Febrile seizures are the most common type of developmental seizures, affect ing up to 5% of children. Experimental complex febrile seizures involving t he immature rat hippocampus led to a persistent lowering of seizure thresho ld despite an upregulation of inhibition. Here we provide a mechanistic res olution to this paradox by showing that, in the hippocampus of rats that ha d febrile seizures, the long-lasting enhancement of the widely expressed in trinsic: membrane conductance I-h converts the potentiated synaptic inhibit ion to hyperexcitability in a frequency-dependent manner. The altered gain of this molecular inhibition-excitation converter reveals a new mechanism f or controlling the balance of excitation-inhibition in the limbic system. I n addition, here we show for the first time that h-channels are modified in a human neurological disease paradigm.