OASIS

Presentation Abstract

Program#/Poster#:	716.12/C29
Title:	Cortical dendritic HCN1 subunit deletion results in enhanced pyramidal cell excitability and epileptogenesis
Location:	South Hall A
Presentation Time:	Wednesday, Oct 21, 2009, 11:00 AM -12:00 PM
Authors:	*M. M. SHAH¹, Z. HUANG¹, M. C. WALKER²; ¹Pharmacol, Sch. of Pharm., London, United Kingdom; ²UCL Inst. of Neurol., London, United Kingdom
Abstract:	Many recent studies (including Shah et al. (2004)) have shown that HCN1 expression is reduced significantly in the entorhinal cortex and hippocampus following the induction of temporal lobe epilepsy (TLE). The significance of this, however, for the manifestation of TLE remains undetermined. To address this question, HCN1 null mice were employed. Status epilepticus was induced in these mice using kainic acid. Adult HCN1 null mice were more susceptible to kainic acid induced seizures (KAS) than wildtype littermate controls. Following termination of KAS with an anticonvulsant, the mice also developed spontaneous behavioural seizures at a significantly more rapid rate than their wildtype littermates. Cell-attached electrophysiological recordings from EC layer III dendrites present in entorhinal-hippocampal slices revealed that the hyperpolarization-activated cation current, I_h was ablated in HCN1-/- neurons. Whole-cell current clamp recordings showed that as a consequence, dendritic input resistance was considerably enhanced in HCN1-/- neurons such that significantly more action potentials could be recorded from these, despite hyperpolarized resting membrane potentials. In addition, the integration of excitatory post-synaptic potentials (EPSPs) was enhanced considerably in HCN1-/- neurons such that at normal resting membrane potential, a 50 Hz train of EPSPs produced action potentials. As a result of this enhanced pyramidal cell excitability, spontaneous EPSC frequency onto HCN1-/- neurons was considerably greater than that onto wildtype cells, resulting in an imbalance between normal excitatory and inhibitory synaptic activity in HCN1-/- slices. These results suggest that dendritic HCN channels critically regulate cortical pyramidal cell excitability and consequently are able to affect neural network activity. Further, these findings suggest that the reduction in dendritic HCN1 subunit expression during epileptogenesis is likely to facilitate the disorder. Reference Shah, M. M. et al. (2004) Neuron, 44, 495-508
Disclosures:	M.M. Shah, None; Z. Huang, None; M.C. Walker, None.
Keyword(s):	DENDRITE
	ENTORHINAL CORTEX
	EXCITABILITY
Support:	MRC New Investigator Award
	Epilepsy Research Foundation UK Project Grant
	Royal Society Project Grant
	[Authors]. [Abstract Title]. Program No. XXX.XX. 2009 Neuroscience Meeting Planner. Chicago, IL: Society for Neuroscience, 2009. Online. 2009 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.


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