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

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 Oct 22

PMID 20962239

Citations 62

Authors

Vincent Paille

Barbara Picconi

Vincenza Bagetta

Veronica Ghiglieri

Carmelo Sgobio

Massimiliano Di Filippo

Maria T Viscomi

Carmela Giampa

Francesca R Fusco

Fabrizio Gardoni

Giorgio Bernardi

Paul Greengard

Monica Di Luca

Paolo Calabresi

Affiliations

Soon will be listed here.

Abstract

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.

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References

Paille V, Henry V, Lescaudron L, Brachet P, Damier P . Rat model of Parkinson's disease with bilateral motor abnormalities, reversible with levodopa, and dyskinesias. Mov Disord. 2007; 22(4):533-9. DOI: 10.1002/mds.21308. View

Choi S, Lovinger D . Decreased frequency but not amplitude of quantal synaptic responses associated with expression of corticostriatal long-term depression. J Neurosci. 1997; 17(21):8613-20. PMC: 6573722. View

Jenner P . Molecular mechanisms of L-DOPA-induced dyskinesia. Nat Rev Neurosci. 2008; 9(9):665-77. DOI: 10.1038/nrn2471. View

Lin Y, Skeberdis V, Francesconi A, Bennett M, Zukin R . Postsynaptic density protein-95 regulates NMDA channel gating and surface expression. J Neurosci. 2004; 24(45):10138-48. PMC: 6730183. DOI: 10.1523/JNEUROSCI.3159-04.2004. View

German D, Manaye K . Midbrain dopaminergic neurons (nuclei A8, A9, and A10): three-dimensional reconstruction in the rat. J Comp Neurol. 1993; 331(3):297-309. DOI: 10.1002/cne.903310302. View

Wang Z, Kai L, Day M, Ronesi J, Yin H, Ding J . Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons. Neuron. 2006; 50(3):443-52. DOI: 10.1016/j.neuron.2006.04.010. View

Kim E, Sheng M . PDZ domain proteins of synapses. Nat Rev Neurosci. 2004; 5(10):771-81. DOI: 10.1038/nrn1517. View

Tang K, Low M, Grandy D, Lovinger D . Dopamine-dependent synaptic plasticity in striatum during in vivo development. Proc Natl Acad Sci U S A. 2001; 98(3):1255-60. PMC: 14741. DOI: 10.1073/pnas.98.3.1255. View

Lee F, Xue S, Pei L, Vukusic B, Chery N, Wang Y . Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Cell. 2002; 111(2):219-30. DOI: 10.1016/s0092-8674(02)00962-5. View

10.

Spruston N, Jaffe D, Williams S, Johnston D . Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events. J Neurophysiol. 1993; 70(2):781-802. DOI: 10.1152/jn.1993.70.2.781. View

11.

McCoy M, Martinez T, Ruhn K, Szymkowski D, Smith C, Botterman B . Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease. J Neurosci. 2006; 26(37):9365-75. PMC: 3707118. DOI: 10.1523/JNEUROSCI.1504-06.2006. View

12.

Calabresi P, Centonze D, Bernardi G . Electrophysiology of dopamine in normal and denervated striatal neurons. Trends Neurosci. 2000; 23(10 Suppl):S57-63. DOI: 10.1016/s1471-1931(00)00017-3. View

13.

Calabresi P, Maj R, Pisani A, Mercuri N, Bernardi G . Long-term synaptic depression in the striatum: physiological and pharmacological characterization. J Neurosci. 1992; 12(11):4224-33. PMC: 6576009. View

14.

Anglade P, Mouatt-Prigent A, Agid Y, Hirsch E . Synaptic plasticity in the caudate nucleus of patients with Parkinson's disease. Neurodegeneration. 1996; 5(2):121-8. DOI: 10.1006/neur.1996.0018. View

15.

Gerfen C, Engber T, Mahan L, Susel Z, Chase T, Monsma Jr F . D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990; 250(4986):1429-32. DOI: 10.1126/science.2147780. View

16.

Calabresi P, Saiardi A, Pisani A, Baik J, Centonze D, Mercuri N . Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. J Neurosci. 1997; 17(12):4536-44. PMC: 6573334. View

17.

Lovinger D, Tyler E, Merritt A . Short- and long-term synaptic depression in rat neostriatum. J Neurophysiol. 1993; 70(5):1937-49. DOI: 10.1152/jn.1993.70.5.1937. View

18.

Hoglinger G, Rizk P, Muriel M, Duyckaerts C, Oertel W, Caille I . Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci. 2004; 7(7):726-35. DOI: 10.1038/nn1265. View

19.

Olsson M, Nikkhah G, Bentlage C, Bjorklund A . Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J Neurosci. 1995; 15(5 Pt 2):3863-75. PMC: 6578238. View

20.

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View