RT Journal Article
SR Electronic
T1 Loss of Dendritic HCN1 Subunits Enhances Cortical Excitability and Epileptogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10979
OP 10988
DO 10.1523/JNEUROSCI.1531-09.2009
VO 29
IS 35
A1 Zhuo Huang
A1 Matthew C. Walker
A1 Mala M. Shah
YR 2009
UL http://www.jneurosci.org/content/29/35/10979.abstract
AB Hyperpolarization-activated cation nonselective 1 (HCN1) plasticity in entorhinal cortical (EC) and hippocampal pyramidal cell dendrites is a salient feature of temporal lobe epilepsy. However, the significance remains undetermined. We demonstrate that adult HCN1 null mice are more susceptible to kainic acid-induced seizures. After termination of these with an anticonvulsant, the mice also developed spontaneous behavioral seizures at a significantly more rapid rate than their wild-type littermates. This greater seizure susceptibility was accompanied by increased spontaneous activity in HCN1−/− EC layer III neurons. Dendritic Ih in these neurons was ablated, too. Consequentially, HCN1−/− dendrites were more excitable, despite having significantly more hyperpolarized resting membrane potentials (RMPs). In addition, the integration of EPSPs was enhanced considerably such that, at normal RMP, a 50 Hz train of EPSPs produced action potentials in HCN1−/− neurons. As a result of this enhanced pyramidal cell excitability, spontaneous EPSC frequency onto HCN1−/− neurons was considerably greater than that onto wild types, causing an imbalance between normal excitatory and inhibitory synaptic activity. These results suggest that dendritic HCN channels are likely to play a critical role in regulating cortical pyramidal cell excitability. Furthermore, these findings suggest that the reduction in dendritic HCN1 subunit expression during epileptogenesis is likely to facilitate the disorder.