Cerebral Cortex Advance Access originally published online on September 15, 2008
Cerebral Cortex 2009 19(4):876-888; doi:10.1093/cercor/bhn135
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Reorganization of Inhibitory Synapses and Increased PSD Length of Perforated Excitatory Synapses in Hippocampal Area CA1 of Dystrophin-Deficient mdx Mice
1 CNRS, Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, UMR 8620, F-91405 Orsay, France, 2 Univ Paris-Sud, Orsay, F-91405, France, 3 Department of Psychology, Psychobiology Area, University of the Balearic Islands, 07122 Palma de Mallorca, Spain, 4 Laboratoire de RMN Biologique, ICSN-CNRS, Avenue de la Terrasse, 91198 Gif sur Yvette, France, 5 Univ Paris-Sud, Centre Commun de Microscopie Electronique (CCME), CNRS, UMR 8080, Orsay, F-91405, France, 6 Current address: Laboratoire de Physique des Solides, UMR 8502, CNRS, Université Paris-Sud 11, F-91405 Orsay, France
Address correspondence to Dr Cyrille Vaillend, Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, CNRS, Université Paris-Sud XI, Bât 446, UMR 8620, F-91405 Orsay cedex, France. Email: cyrille.vaillend{at}u-psud.fr.
Dystrophin is a cytoskeletal membrane-bound protein expressed in both muscle and brain. Brain dystrophin is thought to be involved in the stabilization of 
-aminobutyric acid (GABA)A-receptor (GABAA-R)clusters in postsynaptic densities (PSDs) at inhibitory synapses onto pyramidal cells, and its loss has been linked to cognitive impairments in Duchenne muscular dystrophy. Dystrophin-deficient mdx mice have learning deficits and altered synaptic plasticity in cornu ammonis (CA1) hippocampus, but the possibility that altered synapse morphology or distribution may underlie these alterations has not been examined. Here we used in vivo magnetic resonance imaging and histological analyses to assess brain volumetric and cytoarchitectonic abnormalities and quantitative electron microscopy to evaluate the density and ultrastructure of CA1 hippocampal synapses in mdx mice. We found that mdx mice have increased density of axodendritic symmetric inhibitory synapses and larger PSDs in perforated asymmetric excitatory synapses in the proximal, but not distal, CA1 apical dendrites that normally express dystrophin, in the absence of gross brain malformations. Data are discussed in light of the known molecular and neurophysiological alterations in mdx mice. We suggest that increased inhibitory synapse density reflects tenuous compensation of altered clustering of 
2 subunit–containing GABAA-Rs in CA1 dendrites, whereas increased PSD length in perforated synapses suggests secondary alterations in excitatory synapse organization associated with enhanced synaptic excitation.
Key Words: DMD • MRI • quantitative electron microscopy • stereology • structural plasticity