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Altered synaptic clustering of GABA A receptors in mice lacking dystrophin (mdx mice)
Author(s) -
Knuesel Irene,
Mastrocola Mario,
Zuellig Richard A.,
Bornhauser Beat,
Schaub Marcus C.,
Fritschy JeanMarc
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00887.x
Subject(s) - dystrophin , gephyrin , duchenne muscular dystrophy , neuroscience , postsynaptic potential , biology , cerebellum , mdx mouse , inhibitory postsynaptic potential , utrophin , hippocampus , receptor , postsynaptic density , neurotransmission , microbiology and biotechnology , excitatory postsynaptic potential , glycine receptor , biochemistry , genetics , glycine , amino acid
Dystrophin is selectively localized in the postsynaptic density of neurons in cerebral cortex, hippocampus and cerebellum. Here, we show by double‐immunofluorescence staining that dystrophin is extensively colocalized with GABA A receptor subunit clusters in these brain regions. To determine the relevance of this observation, we investigated in mdx mice, which provide a model of Duchenne muscular dystrophy, whether the absence of dystrophin affects the synaptic clustering of GABA A receptors. A marked reduction in the number of clusters immunoreactive for the α1 and α2 subunits was observed in, respectively, cerebellum and hippocampus of mdx mice, but not in striatum, which is normally devoid of dystrophin. Furthermore, these alterations were not accompanied by a change in gephyrin staining, although gephyrin is colocalized with the majority of GABA A receptor clusters in these regions. These results indicate that dystrophin may play an important role in the clustering or stabilization of GABA A receptors in a subset of central inhibitory synapses. These deficits may underlie the cognitive impairment seen in Duchenne patients.