N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine morphology in striatal medium spiny neurons.
J. Biol. Chem.. 2012-04-09; 287(22): 18103-18114
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1. J Biol Chem. 2012 May 25;287(22):18103-14. doi: 10.1074/jbc.M112.347427. Epub
2012 Apr 9.
N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine
morphology in striatal medium spiny neurons.
Vastagh C(1), Gardoni F, Bagetta V, Stanic J, Zianni E, Giampà C, Picconi B,
Calabresi P, Di Luca M.
(1)Department of Pharmacological Sciences, University of Milano, Milano, Italy.
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.
PMID: 22493505 [Indexed for MEDLINE]