Dystrophin is selectively localized in the postsynaptic density of neurons
in cerebral cortex, hippocampus and cerebellum. Here, we show by double-imm
unofluorescence staining that dystrophin is extensively colocalized with GA
BA(A) receptor subunit clusters in these brain regions. To determine the re
levance of this observation, we investigated in mdx mice, which provide a m
odel of Duchenne muscular dystrophy, whether the absence of dystrophin affe
cts the synaptic clustering of GABA(A) receptors. A marked reduction in the
number of clusters immunoreactive for the alpha 1 and alpha 2 subunits was
observed in, respectively, cerebellum and hippocampus of mdx mice, but not
in striatum, which is normally devoid of dystrophin. Furthermore, these al
terations were not accompanied by a change in gephyrin staining, although g
ephyrin is colocalized with the majority of GABA(A) receptor clusters in th
ese regions. These results indicate that dystrophin may play an important r
ole in the clustering or stabilization of GABA(A) receptors in a subset of
central inhibitory synapses. These deficits may underlie the cognitive impa
irment seen in Duchenne patients.