Impaired Dendritic Expression and Plasticity of h-Channels in the fmr1-/y Mouse Model of Fragile X Syndrome

被引：86

作者：

Brager, Darrin H. ^{[1
]}

Akhavan, Arvin R. ^{[1
]}

Johnston, Daniel ^{[1
]}

机构：

[1] Univ Texas Austin, Ctr Learning & Memory, Austin, TX 78712 USA

来源：

CELL REPORTS | 2012年 / 1卷 / 03期

基金：

美国国家卫生研究院;

关键词：

RAT HIPPOCAMPAL-NEURONS; LONG-TERM POTENTIATION; I-H; MESSENGER-RNAS; CA1; EXCITABILITY; TRANSLATION; MODULATION;

D O I：

10.1016/j.celrep.2012.02.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 Ih occurred in both wildtype and fmr1(-/y) mice, persistent increases in Ih that occurred after LTP induction in wild-type mice were absent in fmr1(-/y) mice. Thus, chronic upregulation of dendritic Ih 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.

引用

页码：225 / 233

页数：9

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