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.
| Original language | English |
|---|---|
| Pages (from-to) | 1979-1993 |
| Number of pages | 15 |
| Journal | European Journal of Neuroscience |
| Volume | 29 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - May 2009 |
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Keywords
- Dorsolateral striatum
- Fast-spiking interneurons
- Postsynaptic density
- Scaffolding proteins
- Synaptic plasticity
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Epilepsy-induced abnormal striatal plasticity in Bassoon mutant mice. / Ghiglieri, Veronica; Picconi, Barbara; Sgobio, Carmelo; Bagetta, Vincenza; Barone, Ilaria; Paillè, Vincent; Di Filippo, Massimiliano; Polli, Federica; Gardoni, Fabrizio; Altrock, Wilko; Gundelfinger, Eckart D.; De Sarro, Giovambattista; Bernardi, Giorgio; Ammassari-Teule, Martine; Di Luca, Monica; Calabresi, Paolo.
In: European Journal of Neuroscience, Vol. 29, No. 10, 05.2009, p. 1979-1993.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Epilepsy-induced abnormal striatal plasticity in Bassoon mutant mice
AU - Ghiglieri, Veronica
AU - Picconi, Barbara
AU - Sgobio, Carmelo
AU - Bagetta, Vincenza
AU - Barone, Ilaria
AU - Paillè, Vincent
AU - Di Filippo, Massimiliano
AU - Polli, Federica
AU - Gardoni, Fabrizio
AU - Altrock, Wilko
AU - Gundelfinger, Eckart D.
AU - De Sarro, Giovambattista
AU - Bernardi, Giorgio
AU - Ammassari-Teule, Martine
AU - Di Luca, Monica
AU - Calabresi, Paolo
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Dorsolateral striatum
KW - Fast-spiking interneurons
KW - Postsynaptic density
KW - Scaffolding proteins
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=65749116371&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65749116371&partnerID=8YFLogxK
U2 - 10.1111/j.1460-9568.2009.06733.x
DO - 10.1111/j.1460-9568.2009.06733.x
M3 - Article
C2 - 19453636
AN - SCOPUS:65749116371
VL - 29
SP - 1979
EP - 1993
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
SN - 0953-816X
IS - 10
ER -