Impaired Dendritic Expression and Plasticity Of H-Channels in the fmr1(-/Y) Mouse Model of Fragile X Syndrome

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Date

2012-03

Authors

Brager, Darrin H.
Akhavan, Arvin R.
Johnston, Daniel

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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 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.

Department

Center for Learning and Memory

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Keywords

mental-retardation protein, ca1 pyramidal neurons, rat, hippocampal-neurons, temporal-lobe epilepsy, long-term potentiation, i-h, messenger-rnas, excitability, translation, modulation, cell biology

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Citation

Brager, Darrin H., Arvin R. Akhavan, and Daniel Johnston. "Impaired dendritic expression and plasticity of h-channels in the fmr1?/y mouse model of fragile X syndrome." Cell reports, Vol. 1, No. 3 (Mar., 2012): 225-233.

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http://hdl.handle.net/2152/43236

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