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

Cell Rep. 2012 Mar 29;1(3):225-33. doi: 10.1016/j.celrep.2012.02.002.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / physiopathology
  • Cyclic Nucleotide-Gated Cation Channels / metabolism*
  • Dendrites / metabolism*
  • Disease Models, Animal
  • Fragile X Mental Retardation Protein / metabolism*
  • Fragile X Syndrome / metabolism*
  • Fragile X Syndrome / physiopathology*
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • In Vitro Techniques
  • Ion Channel Gating
  • Ion Channels / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Neuronal Plasticity*
  • Potassium Channels / metabolism*
  • Receptors, Metabotropic Glutamate

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Hcn1 protein, mouse
  • Hcn2 protein, mouse
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ion Channels
  • Potassium Channels
  • Receptors, Metabotropic Glutamate
  • Fragile X Mental Retardation Protein