Distinct Levels of Dopamine Denervation Differentially Alter Striatal Synaptic Plasticity and NMDA Receptor Subunit Composition

被引：144

作者：

Paille, Vincent ^{[2
]}

Picconi, Barbara ^{[2
]}

Bagetta, Vincenza ^{[2
]}

Ghiglieri, Veronica ^{[2
]}

Sgobio, Carmelo ^{[2
]}

Di Filippo, Massimiliano ^{[2
]}

Viscomi, Maria T. ^{[2
]}

Giampa, Carmela ^{[2
]}

Fusco, Francesca R. ^{[2
]}

Gardoni, Fabrizio ^{[3
]}

Bernardi, Giorgio ^{[2
]}

Greengard, Paul ^{[4
]}

Di Luca, Monica ^{[3
]}

Calabresi, Paolo ^{[1
,2
]}

机构：

[1] Univ Perugia, Neurol Clin, Dipartimento Specialita Med Chirurg & Sanita Pubb, Osped S Maria della Misericordia, I-06156 Perugia, Italy

[2] Fdn Santa Lucia, Inst Ricovero & Cura Carattere Sci, I-00179 Rome, Italy

[3] Univ Milan, Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy

[4] Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10065 USA

来源：

JOURNAL OF NEUROSCIENCE | 2010年 / 30卷 / 42期

关键词：

LONG-TERM DEPRESSION; PROTEIN-KINASE-II; PARKINSONS-DISEASE; INDUCED DYSKINESIA; STRIATOPALLIDAL NEURONS; MOLECULAR-MECHANISMS; 6-OHDA LESIONS; MOTOR DEFICITS; VOLTAGE-CLAMP; NR2A SUBUNIT;

D O I：

10.1523/JNEUROSCI.2149-10.2010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

A correct interplay between dopamine (DA) and glutamate is essential for corticostriatal synaptic plasticity and motor activity. In an experimental model of Parkinson's disease (PD) obtained in rats, the complete depletion of striatal DA, mimicking advanced stages of the disease, results in the loss of both forms of striatal plasticity: long-term potentiation (LTP) and long-term depression (LTD). However, early PD stages are characterized by an incomplete reduction in striatal DA levels. The mechanism by which this incomplete reduction in DA level affects striatal synaptic plasticity and glutamatergic synapses is unknown. Here we present a model of early PD in which a partial denervation, causing mild motor deficits, selectively affects NMDA-dependent LTP but not LTD and dramatically alters NMDA receptor composition in the postsynaptic density. Our findings show that DA decrease influences corticostriatal synaptic plasticity depending on the level of depletion. The use of the TAT2A cell-permeable peptide, as an innovative therapeutic strategy in early PD, rescues physiological NMDA receptor composition, synaptic plasticity, and motor behavior.

引用

页码：14182 / 14193

页数：12

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