Downregulation of tonic GABAergic inhibition in a mouse model of fragile X syndrome

Giulia Curia, Thomas Papouin, Philippe Séguéla, Massimo Avoli

Research output: Contribution to journalArticlepeer-review

170 Scopus citations

Abstract

The absence of fragile X mental retardation protein results in the fragile X syndrome (FXS), a common form of mental retardation associated with attention deficit, autistic behavior, and epileptic seizures. The phenotype of FXS is reproduced in fragile X mental retardation 1 (fmr1) knockout (KO) mice that have region-specific altered expression of some γ-aminobutyric acid (GABAA) receptor subunits. However, little is known about the characteristics of GABAergic inhibition in the subiculum of these animals. We employed patch-clamp recordings from subicular pyramidal cells in an in vitro slice preparation. In addition, semiquantitative polymerase chain reaction and western blot experiments were performed on subiculum obtained from wild-type (WT) and KO mice. We found that tonic GABAA currents were downregulated in fmr1 KO compared with WT neurons, whereas no significant differences were observed in phasic GABAA currents. Molecular biology analysis revealed that the tonic GABAA receptor subunits α5 and δ were underexpressed in the fmr1 KO mouse subiculum compared with WT. Because the subiculum plays a role in both cognitive functions and epileptic disorders, we propose that altered tonic inhibition in this structure contributes to the behavioral deficits and epileptic activity seen in FXS patients. This conclusion is in line with evidence implicating tonic GABAA inhibition in learning and memory.

Original languageEnglish
Pages (from-to)1515-1520
Number of pages6
JournalCerebral Cortex
Volume19
Issue number7
DOIs
StatePublished - Jul 2009

Keywords

  • Fragile X
  • GABA
  • Patch-clamp
  • Subiculum
  • Tonic inhibition

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