UC Irvine

Upregulated H-Current in Hyperexcitable CA1 Dendrites after Febrile Seizures. Dyhrfjeld-Johnsen J, Morgan RJ, Csaba Foldy, Soltesz I., Front Cell Neurosci. 2008;2:2. doi:10.3389/neuro.03.002.2008. 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. HCN Hyperpolarization-Activated Cation Channels Inhibit EPSPs by Interactions with M-type K + Channels. George MS, Abbott LF, Siegelbaum SA. Nat Neurosci 2009;12(5):577–584. The processing of synaptic potentials by neuronal dendrites depends on both their passive cable properties and active voltage-gated channels, which can generate complex effects as a result of their nonlinear properties. We characterized the actions of HCN (hyperpolarization-activated cyclic nucleotide-gated cation) channels on dendritic processing of subthreshold excitatory postsynaptic potentials (EPSPs) in mouse CA1 hippocampal neurons. The HCN channels generated an excitatory inward current ( I h ) that exerted a direct depolarizing effect on the peak voltage of weak EPSPs, but produced a paradoxical hyperpolarizing effect on the peak voltage of stronger, but still subthreshold, EPSPs. Using a combined modeling and experimental approach, we found that the inhibitory action of I h was caused by its interaction with the delayed-rectifier M-type K + current. In this manner, I h can enhance spike firing in response to an EPSP when spike threshold is low and can inhibit firing when spike threshold is high.