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.
Highlights
An interplay between dopamine (DA) and NMDA receptors in striatum is essential to drive motor behavior
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
Even if it is known that alterations of NMDA receptor composition at the corticostriatal synapse contribute to the clinical features of disease states, i.e. Parkinson disease (PD) and Huntington disease (18 –20), the possible functional and morphological outcome of NMDA receptor subunit composition in dendritic spines of medium spiny neurons (MSNs) still remains unclear
Summary
An interplay between dopamine (DA) and NMDA receptors in striatum is essential to drive motor behavior. 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 to the clinical features of disease states such as experimental parkinsonism but leads to a functional and morphological outcome in dendritic spines of medium spiny neurons. Recent reports have suggested that NR2A and NR2B subunits differentially sculpt glutamatergic inputs in striatal MSNs [10]; pharmacological blockade of NR2A and NR2B subunits affects the amplitude and kinetics of NMDA responses and produces contrasting effects on D1 receptor modulation [10] In this context, even if it is known that alterations of NMDA receptor composition at the corticostriatal synapse contribute to the clinical features of disease states, i.e. PD and Huntington disease (18 –20), the possible functional and morphological outcome of NMDA receptor subunit composition in dendritic spines of MSNs still remains unclear. Treatment with NR2A antagonist or with NR2A blocking peptide induces morphological modifications of dendritic spines as induced by D1 receptor activation
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