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Comment
. 2009 Jul;19(7):1490-2.
doi: 10.1093/cercor/bhp089. Epub 2009 Apr 22.

Fragile X mental retardation protein in the driver's seat

Jay E Brenman  1
Affiliations
Comment

Fragile X mental retardation protein in the driver's seat

Jay E Brenman. Cereb Cortex. 2009 Jul.
No abstract available

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Figures

Figure 1.
Figure 1.
Summary of the major findings presented by Curia et al. and Qiu et al. in this issue of Cerebral Cortex. Data from these two papers place FMRP, the protein product of the FMR1 gene mutated in FXS in the driver's seat, controlling the “brakes” and “gas” of inhibition and excitation in hippocampal and parahippocampal circuits. Together, the papers show that fmr1 knockout (KO) mice, an animal model for FXS, have decreased inhibition (the brakes) but increased excitability (the “accelerator” or the “gas”) compared with wild type (WT) mice. Neuronal excitability braking mechanisms (red arrows) are generally decreased in fmr1 knockout mice primarily by decreased GABA effectiveness, whereas increased excitability (green arrows) occurs due to modulation of signaling via the metabotropic glutamate receptor, mGluR5. Curia et al., and Qiu et al. suggest that these changes may be limited to hippocampal and parahippocampal cortices, perhaps suggesting a local pathogenic mechanism for increased seizure susceptibility in FXS.
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