| First Author | Huang Z | Year | 2009 |
| Journal | J Neurosci | Volume | 29 |
| Issue | 35 | Pages | 10979-88 |
| PubMed ID | 19726656 | Mgi Jnum | J:152452 |
| Mgi Id | MGI:4358800 | Doi | 10.1523/JNEUROSCI.1531-09.2009 |
| Citation | Huang Z, et al. (2009) Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis. J Neurosci 29(35):10979-88 |
| abstractText | 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. |
