Reorganization of inhibitory synapses and increased PSD length of perforated excitatory synapses in hippocampal area CA1 of dystrophin-deficient mdx mice.
Dystrophin is a cytoskeletal membrane-bound protein expressed in both muscle and brain. Brain dystrophin is thought to be involved in the stabilization of gamma-aminobutyric acid (GABA)(A)-receptor (GABA(A)-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 alpha2 subunit-containing GABA(A)-Rs in CA1 dendrites, whereas increased PSD length in perforated synapses suggests secondary alterations in excitatory synapse organization associated with enhanced synaptic excitation.
Miranda
R
R
CNRS, Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, UMR, Orsay, France.
Sébrié
C
C
Degrouard
J
J
Gillet
B
B
Jaillard
D
D
Laroche
S
S
Vaillend
C
C
D000818:Animals; D001369:Axons / Q000473:pathology; D003712:Dendrites / Q000473:pathology; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008817:Mice, Mutant Strains; D009433:Neural Inhibition / Q000235:genetics; D013569:Synapses / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure
D016189:Dystrophin