Dendritic spines of medium spiny neurons represent an essential site of information processing between NMDA and dopamine receptors in striatum. Even if activation of NMDA receptors in the striatum has important implications for synaptic plasticity and disease states, the contribution of specific NMDA receptor subunits still remains to be elucidated. Here, we show that treatment of corticostriatal slices with NR2A antagonist NVP-AAM077 or with NR2A blocking peptide induces a significant increase of spine head width. Sustained treatment with D1 receptor agonist (SKF38393) leads to a significant decrease of NR2A-containing NMDA receptors and to a concomitant increase of spine head width. Interestingly, co-treatment of corticostriatal slices with NR2A antagonist (NVP-AAM077) and D1 receptor agonist augmented the increase of dendritic spine head width as obtained with SKF38393. Conversely, NR2B antagonist (ifenprodil) blocked any morphological effect induced by D1 activation. These results indicate that alteration of NMDA receptor composition at the corticostriatal synapse contributes not only to the clinical features of disease states such as experimental parkinsonism but leads also to a functional and morphological outcome in dendritic spines of medium spiny neurons.

N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine morphology in striatal medium spiny neurons / C. Vastagh, F. Gardoni, V. Bagetta, J. Stanic, E. Zianni, C. Giampà, B. Picconi, P. Calabresi, M.M.G. Di Luca. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 287:22(2012), pp. 18103-18114.

N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine morphology in striatal medium spiny neurons

F. Gardoni
Secondo
;
J. Stanic;E. Zianni;M.M.G. Di Luca
Ultimo
2012

Abstract

Dendritic spines of medium spiny neurons represent an essential site of information processing between NMDA and dopamine receptors in striatum. Even if activation of NMDA receptors in the striatum has important implications for synaptic plasticity and disease states, the contribution of specific NMDA receptor subunits still remains to be elucidated. Here, we show that treatment of corticostriatal slices with NR2A antagonist NVP-AAM077 or with NR2A blocking peptide induces a significant increase of spine head width. Sustained treatment with D1 receptor agonist (SKF38393) leads to a significant decrease of NR2A-containing NMDA receptors and to a concomitant increase of spine head width. Interestingly, co-treatment of corticostriatal slices with NR2A antagonist (NVP-AAM077) and D1 receptor agonist augmented the increase of dendritic spine head width as obtained with SKF38393. Conversely, NR2B antagonist (ifenprodil) blocked any morphological effect induced by D1 activation. These results indicate that alteration of NMDA receptor composition at the corticostriatal synapse contributes not only to the clinical features of disease states such as experimental parkinsonism but leads also to a functional and morphological outcome in dendritic spines of medium spiny neurons.
Settore BIO/14 - Farmacologia
2012
Article (author)
File in questo prodotto:
File Dimensione Formato  
J. Biol. Chem.-2012-Vastagh-18103-14.pdf

Open Access dal 30/10/2013

Tipologia: Pre-print (manoscritto inviato all'editore)
Dimensione 2.59 MB
Formato Adobe PDF
2.59 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/211209
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 35
  • ???jsp.display-item.citation.isi??? 31
social impact