title: N-methyl-D-aspartate (NMDA) receptor composition modulates dendritic spine morphology in striatal medium spiny neurons.
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.
authors.affiliation: Department of Pharmacological Sciences, University of Milano, Milano, Italy.
authors.forename: Csaba
authors.initials: C
authors.lastname: Vastagh
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.forename: Vincenza
authors.initials: V
authors.lastname: Bagetta
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stanic
authors.forename: Elisa
authors.initials: E
authors.lastname: Zianni
authors.forename: Carmen
authors.initials: C
authors.lastname: Giampà
authors.forename: Barbara
authors.initials: B
authors.lastname: Picconi
authors.forename: Paolo
authors.initials: P
authors.lastname: Calabresi
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D018491:Dopamine Agonists; C120997:NR2A NMDA receptor; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate