title: GABAergic miniature spontaneous activity is increased in the CA1 hippocampal region of dystrophic mdx mice.
abstract: Duchenne muscular dystrophy (DMD), a genetic disease due to dystrophin gene mutation and characterised by skeletal muscle failure, is associated with non-progressive cognitive deficits. In human and mouse brain, full-length dystrophin is localised postsynaptically in neocortical, hippocampal and cerebellar neurons. Evidence obtained in the CNS of dystrophic mice (mdx) suggested alterations of the GABAergic system. However, a direct functional evaluation of GABAergic synaptic transmission in mdx mice has not been conducted in the hippocampus, which is involved in cognitive processes and is rich in full-length dystrophin. Here, we investigated evoked and miniature inhibitory postsynaptic currents (IPSCs) in CA1 pyramidal neurons of mdx mice with patch clamp recording techniques. Results showed an increased frequency of miniature spontaneous IPSCs in mdx mice compared with controls, whereas evoked IPSCs did not show significant variations. Paired-pulse facilitation (PPF) analysis showed lack of facilitation at short intervals in mdx mice compared with that in wild-type mice. Analysis of density of synapses that innervate CA1 pyramidal cell bodies did not indicate significant differences between mdx mice and controls. Therefore, we suggest that increased miniature spontaneous IPSC frequency is due to altered pre-synaptic release probability. The present findings are discussed in the light of the accrued evidence for alterations of inhibitory synaptic transmission in the brain of dystrophic mice.
authors.affiliation: Department of Molecular Pathology and Innovative Therapies, Marche Polytechnic University, Ancona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Graciotti
authors.forename: Andrea
authors.initials: A
authors.lastname: Minelli
authors.forename: Diego
authors.initials: D
authors.lastname: Minciacchi
authors.forename: Antonio
authors.initials: A
authors.lastname: Procopio
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fulgenzi
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D008854:Microscopy, Electron; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology / Q000648:ultrastructure; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid