Upregulated H-Current in Hyperexcitable CA1 Dendrites after Febrile Seizures

Abstract

Somatic recordings from CA1 pyramidal cells indicated a persistent upregulation of the h-current ( I _h) after experimental febrile seizures. Here, we examined febrile seizure-induced long-term changes in I _h and neuronal excitability in CA1 dendrites. Cell-attached recordings showed that dendritic I _h was significantly upregulated, with a depolarized half-activation potential and increased maximal current. Although enhanced I _h is typically thought to be associated with decreased dendritic excitability, whole-cell dendritic recordings revealed a robust increase in action potential firing after febrile seizures. We turned to computational simulations to understand how the experimentally observed changes in I _h influence dendritic excitability. Unexpectedly, the simulations, performed in three previously published CA1 pyramidal cell models, showed that the experimentally observed increases in I _h resulted in a general enhancement of dendritic excitability, primarily due to the increased I _h-induced depolarization of the resting membrane potential overcoming the excitability-depressing effects of decreased dendritic input resistance. Taken together, these experimental and modeling results reveal that, contrary to the exclusively anti-convulsive role often attributed to increased I _h in epilepsy, the enhanced I _h can co-exist with, and possibly even contribute to, persistent dendritic hyperexcitability following febrile seizures in the developing hippocampus.