Altered synaptic clustering of GABA(A) receptors in mice lacking dystrophin (mdx mice)

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.