Abnormal Striatal GABA Transmission in the Mouse Model for the Fragile X Syndrome

Diego Centonze, Silvia Rossi, Valentina Mercaldo, Ilaria Napoli, Maria Teresa Ciotti, Valentina De Chiara, Alessandra Musella, Chiara Prosperetti, Paolo Calabresi, Giorgio Bernardi, Claudia Bagni

Research output: Contribution to journalArticle

Abstract

Background: Structural and functional neuroimaging studies suggest abnormal activity in the striatum of patients with the fragile X syndrome (FXS), the most common form of inherited mental retardation. Methods: Neurophysiological and immunofluorescence experiments in striatal brain slices. We studied the synaptic transmission in a mouse model for FXS, as well as the subcellular localization of fragile X mental retardation protein (FMRP) and brain cytoplasmic (BC1) RNA in striatal axons. Results: Our results show that absence of FMRP is associated with apparently normal striatal glutamate-mediated transmission, but abnormal γ-aminobutyric acid (GABA) transmission. This effect is likely secondary to increased transmitter release from GABAergic nerve terminals. We detected the presence of FMRP in axons of striatal neurons and observed a selective increase in the frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs, mIPSCs) in fmr1-knockout mice. We also observed reduced paired-pulse ratio of evoked IPSCs, a finding that is consistent with the idea that transmitter release probability from striatal GABAergic nerve terminals is higher than normal in these mutants. Finally, we have identified the small noncoding BC1 RNA as a critical coplayer of FMRP in the regulation of striatal synaptic transmission. Conclusions: Understanding the physiologic action of FMRP and the synaptic defects associated with GABA transmission might be useful to design appropriate pharmacologic interventions for FXS.

Original languageEnglish
Pages (from-to)963-973
Number of pages11
JournalBiological Psychiatry
Volume63
Issue number10
DOIs
Publication statusPublished - May 15 2008

Keywords

  • BC1 RNA
  • electrophysiology
  • EPSC
  • fragile X mental retardation protein
  • mRNA
  • synaptic plasticity

ASJC Scopus subject areas

  • Biological Psychiatry

Fingerprint Dive into the research topics of 'Abnormal Striatal GABA Transmission in the Mouse Model for the Fragile X Syndrome'. Together they form a unique fingerprint.

  • Cite this

    Centonze, D., Rossi, S., Mercaldo, V., Napoli, I., Ciotti, M. T., De Chiara, V., Musella, A., Prosperetti, C., Calabresi, P., Bernardi, G., & Bagni, C. (2008). Abnormal Striatal GABA Transmission in the Mouse Model for the Fragile X Syndrome. Biological Psychiatry, 63(10), 963-973. https://doi.org/10.1016/j.biopsych.2007.09.008