| Abstract No.: | B-B2035 |
| Country: | Canada |
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| Title: | DOWNREGULATION OF TONIC GABAA RECEPTOR-MEDIATED INHIBITION IN A MOUSE MODEL OF FRAGILE X SYNDROME |
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| Authors/Affiliations: | 1 Giulia Curia*; 1 Thomas Papouin; 1 Philippe Séguéla; 1 Massimo Avoli;
1 Montreal Neurological Institute, Departments of Neurology & Neurosurgery, McGill University, QC, Canada
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| Content: | Objectives - The absence of fragile X mental retardation protein (FMRP) results in the fragile X syndrome (FXS), a common form of mental retardation associated with attention deficit, autistic behavior and epileptic seizures. The neurologic phenotype of FXS is reproduced in fmr1 knockout (KO) mice that have region specific, altered expression of several GABAA receptor subunits at both messenger and protein level. Little is however known about the functional characteristics of inhibition in these mice. We tested the hypothesis that GABAA receptor-mediated currents are altered in the fmr1 KO mice subiculum.
Materials and Methods - We employed whole-cell patch-clamp recordings, from subicular pyramidal-like cells in an in vitro slice preparation. In addition, real-time RT-PCR and western blot experiments were carried out on subiculum obtained from wild type (WT) and fmr1 KO mice.
Results - We found that the tonic GABAA receptor-mediated current density was downregulated by ~91% in fmr1 KO compared to WT neurons (WT: 5.32±0.88 pA/pF, n= 7 neurons; fmr1 KO: 0.48±0.13 pA/pF, n= 7), while no significant differences were observed with phasic GABAA receptor-mediated currents. Real-time RT-PCR and western blot analysis revealed that the tonic GABAA receptor subunits α5 and δ were under-expressed in the fmr1 KO mouse subiculum (α5: R= 0.74±0.03, n=4 mice; DR= 87±4.6%, n= 4; δ: R= 0.65±0.06, n= 4; DR= 72±9.0%, n= 4).
Conclusion - Since the subiculum plays a role in both cognitive functions and epileptic disorders we propose that altered tonic inhibition contributes to the behavioral deficits and epileptic activity seen in FXS patients.
[Supported by: CIHR, FXRFC, CURE and Savoy Foundation]
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