title: Epilepsy-induced abnormal striatal plasticity in Bassoon mutant mice.
abstract: Recently, the striatum has been implicated in the spread of epileptic seizures. As the absence of functional scaffolding protein Bassoon in mutant mice is associated with the development of pronounced spontaneous seizures, we utilized this new genetic model of epilepsy to investigate seizure-induced changes in striatal synaptic plasticity. Mutant mice showed reduced long-term potentiation in striatal spiny neurons, associated with an altered N-methyl-D-aspartate (NMDA) receptor subunit distribution, whereas GABAergic fast-spiking (FS) interneurons showed NMDA-dependent short-term potentiation that was absent in wild-type animals. Alterations in the dendritic morphology of spiny neurons and in the number of FS interneurons were also observed. Early antiepileptic treatment with valproic acid reduced epileptic attacks and mortality, rescuing physiological striatal synaptic plasticity and NMDA receptor subunit composition. However, morphological alterations were not affected by antiepileptic treatment. Our results indicate that, in Bsn mutant mice, initial morphological alterations seem to reflect a more direct effect of the abnormal genotype, whereas plasticity changes are likely to be caused by the occurrence of repeated cortical seizures.
authors.affiliation: Laboratorio di Neurofisiologia, Fondazione Santa Lucia, IRCCS c/o CERC, Rome, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ghiglieri
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Carmelo
authors.initials: C
authors.lastname: Sgobio
authors.forename: Vincenza
authors.initials: V
authors.lastname: Bagetta
authors.forename: Ilaria
authors.initials: I
authors.lastname: Barone
authors.forename: Vincent
authors.initials: V
authors.lastname: Paillè
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Di Filippo
authors.forename: Federica
authors.initials: F
authors.lastname: Polli
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Wilko
authors.initials: W
authors.lastname: Altrock
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Martine
authors.initials: M
authors.lastname: Ammassari-Teule
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques
chemical_list: C498441:Bsn protein, mouse; D009419:Nerve Tissue Proteins