Epilepsy-induced abnormal striatal plasticity in Bassoon mutant mice.
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.
Ghiglieri
Veronica
V
Laboratorio di Neurofisiologia, Fondazione Santa Lucia, IRCCS c/o CERC, Rome, Italy.
Picconi
Barbara
B
Sgobio
Carmelo
C
Bagetta
Vincenza
V
Barone
Ilaria
I
Paillè
Vincent
V
Di Filippo
Massimiliano
M
Polli
Federica
F
Gardoni
Fabrizio
F
Altrock
Wilko
W
Gundelfinger
Eckart D
ED
De Sarro
Giovambattista
G
Bernardi
Giorgio
G
Ammassari-Teule
Martine
M
Di Luca
Monica
M
Calabresi
Paolo
P
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
C498441:Bsn protein, mouse; D009419:Nerve Tissue Proteins