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Inherited cortical HCN1 channel loss amplifies dendritic calcium electrogenesis and burst firing in a rat absence epilepsy model
Author(s) -
Kole Maarten H.P.,
Bräuer Anja U.,
Stuart Greg J.
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.122028
Subject(s) - bursting , soma , neuroscience , dendritic spine , hcn channel , pyramidal cell , chemistry , apical dendrite , population , dendrite (mathematics) , epilepsy , cortex (anatomy) , biology , ion channel , receptor , hippocampal formation , medicine , biochemistry , geometry , environmental health , mathematics
While idiopathic generalized epilepsies are thought to evolve from temporal highly synchronized oscillations between thalamic and cortical networks, their cellular basis remains poorly understood. Here we show in a genetic rat model of absence epilepsy (WAG/Rij) that a rapid decline in expression of hyperpolarization‐activated cyclic‐nucleotide gated (HCN1) channels ( I h ) precedes the onset of seizures, suggesting that the loss of HCN1 channel expression is inherited rather than acquired. Loss of HCN1 occurs primarily in the apical dendrites of layer 5 pyramidal neurons in the cortex, leading to a spatially uniform 2‐fold reduction in dendritic HCN current throughout the entire somato‐dendritic axis. Dual whole‐cell recordings from the soma and apical dendrites demonstrate that loss of HCN1 increases somato‐dendritic coupling and significantly reduces the frequency threshold for generation of dendritic Ca 2+ spikes by backpropagating action potentials. As a result of increased dendritic Ca 2+ electrogenesis a large population of WAG/Rij layer 5 neurons showed intrinsic high‐frequency burst firing. Using morphologically realistic models of layer 5 pyramidal neurons from control Wistar and WAG/Rij animals we show that the experimentally observed loss of dendritic I h recruits dendritic Ca 2+ channels to amplify action potential‐triggered dendritic Ca 2+ spikes and increase burst firing. Thus, loss of function of dendritic HCN1 channels in layer 5 pyramidal neurons provides a somato‐dendritic mechanism for increasing the synchronization of cortical output, and is therefore likely to play an important role in the generation of absence seizures.