Impaired dendritic expression and plasticity of h-channels in the fmr1(-/y) mouse model of fragile X syndrome.
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.
Center for Learning and Memory, The University of Texas at Austin, Austin, TX 78712, USA. dbrager@mail.clm.utexas.edu
Darrin H
DH
Brager
Arvin R
AR
Akhavan
Daniel
D
Johnston
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000503:physiopathology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism*; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity; D015221:Potassium Channels / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate
D054815:Cyclic Nucleotide-Gated Cation Channels; D051860:Fragile X Messenger Ribonucleoprotein 1; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; C578666:Hcn1 protein, mouse; C578711:Hcn2 protein, mouse