Referenced in: none

Automatically associated channels: HCN1 , HCN2

Title: Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse model of fragile X syndrome.

Authors: Darrin H Brager, Arvin R Akhavan, Daniel Johnston

Journal, date & volume: Cell Rep, 2012 Mar 29 , 1, 225-33

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22662315

Abstract
Despite extensive research into both synaptic and morphological changes, surprisingly little is known about dendritic function in fragile X syndrome (FXS). We found that the dendritic input resistance of CA1 neurons was significantly lower in fmr1(-/y) versus wild-type mice. Consistent with elevated dendritic I(h), voltage sag, rebound, and resonance frequency were significantly higher and temporal summation was lower in the dendrites of fmr1(-/y) mice. Dendritic expression of the h-channel subunit HCN1, but not HCN2, was higher in the CA1 region of fmr1(-/y) mice. Interestingly, whereas mGluR-mediated persistent decreases in I(h) occurred in both wildtype and fmr1(-/y) mice, persistent increases in I(h) that occurred after LTP induction in wild-type mice were absent in fmr1(-/y) mice. Thus, chronic upregulation of dendritic I(h) in conjunction with impairment of homeostatic h-channel plasticity represents a dendritic channelopathy in this model of mental retardation and may provide a mechanism for the cognitive impairment associated with FXS.