Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors

Paolo Calabresi, Adolfo Saiardi, Antonio Pisani, Ja-Hyun Baik, Diego Centonze, Nicola B. Mercuri, Giorgio Bernardi, Emiliana Borrelli

Research output: Contribution to journalArticle

219 Citations (Scopus)

Abstract

Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.

Original languageEnglish
Pages (from-to)4536-4544
Number of pages9
JournalJournal of Neuroscience
Volume17
Issue number12
Publication statusPublished - 1997 Jun 24
Externally publishedYes

Fingerprint

Neuronal Plasticity
Long-Term Potentiation
Corpus Striatum
N-Methyl-D-Aspartate Receptors
Parkinson Disease
Sulpiride
Dopamine D2 Receptors
Excitatory Postsynaptic Potentials
Movement Disorders
Automatic Data Processing
Synapses
Magnesium
mouse DRD2 protein
Phenotype
Genes

Keywords

  • D2 receptor knock-out mice
  • Dopamine
  • Dopamine D2 receptor
  • LTD
  • LTP
  • NMDA
  • Striatum
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Calabresi, P., Saiardi, A., Pisani, A., Baik, J-H., Centonze, D., Mercuri, N. B., ... Borrelli, E. (1997). Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. Journal of Neuroscience, 17(12), 4536-4544.

Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. / Calabresi, Paolo; Saiardi, Adolfo; Pisani, Antonio; Baik, Ja-Hyun; Centonze, Diego; Mercuri, Nicola B.; Bernardi, Giorgio; Borrelli, Emiliana.

In: Journal of Neuroscience, Vol. 17, No. 12, 24.06.1997, p. 4536-4544.

Research output: Contribution to journalArticle

Calabresi, P, Saiardi, A, Pisani, A, Baik, J-H, Centonze, D, Mercuri, NB, Bernardi, G & Borrelli, E 1997, 'Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors', Journal of Neuroscience, vol. 17, no. 12, pp. 4536-4544.
Calabresi P, Saiardi A, Pisani A, Baik J-H, Centonze D, Mercuri NB et al. Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. Journal of Neuroscience. 1997 Jun 24;17(12):4536-4544.
Calabresi, Paolo ; Saiardi, Adolfo ; Pisani, Antonio ; Baik, Ja-Hyun ; Centonze, Diego ; Mercuri, Nicola B. ; Bernardi, Giorgio ; Borrelli, Emiliana. / Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. In: Journal of Neuroscience. 1997 ; Vol. 17, No. 12. pp. 4536-4544.
@article{984e566c60534a9b9743142dd404f0db,
title = "Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors",
abstract = "Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.",
keywords = "D2 receptor knock-out mice, Dopamine, Dopamine D2 receptor, LTD, LTP, NMDA, Striatum, Synaptic plasticity",
author = "Paolo Calabresi and Adolfo Saiardi and Antonio Pisani and Ja-Hyun Baik and Diego Centonze and Mercuri, {Nicola B.} and Giorgio Bernardi and Emiliana Borrelli",
year = "1997",
month = "6",
day = "24",
language = "English",
volume = "17",
pages = "4536--4544",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "12",

}

TY - JOUR

T1 - Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors

AU - Calabresi, Paolo

AU - Saiardi, Adolfo

AU - Pisani, Antonio

AU - Baik, Ja-Hyun

AU - Centonze, Diego

AU - Mercuri, Nicola B.

AU - Bernardi, Giorgio

AU - Borrelli, Emiliana

PY - 1997/6/24

Y1 - 1997/6/24

N2 - Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.

AB - Dopamine D2 receptors (D2Rs) are of crucial importance in the striatal processing of motor information received from the cortex. Disruption of the D2R gene function in mice results in a severe locomotor impairment. This phenotype has analogies with Parkinson's disease symptoms. D2R-null mice were used to investigate the role of this receptor in the generation of striatal synaptic plasticity. Tetanic stimulation of corticostriatal fibers produced long-term depression (LTD) of EPSPs in slices from wild-type (WT) mice. Strikingly, recordings from D2R-null mice showed the converse: long-term potentiation (LTP). This LTP, unlike LTD, was blocked by an NMDA receptor antagonist. In magnesium-free medium, LTP was also revealed in WT mice and found to be enhanced by L-sulpiride, a D2R antagonist, whereas it was reversed into LTD by LY 17555, a D2R agonist. In D2R-null mice this modulation was lost. Thus, our study indicates that D2Rs play a key role in mechanisms underlying the direction of long-term changes in synaptic efficacy in the striatum. It also shows that an imbalance between D2R and NMDA receptor activity induces altered synaptic plasticity at corticostriatal synapses. This abnormal synaptic plasticity might cause the movement disorders observed in Parkinson's disease.

KW - D2 receptor knock-out mice

KW - Dopamine

KW - Dopamine D2 receptor

KW - LTD

KW - LTP

KW - NMDA

KW - Striatum

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=0030919907&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030919907&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 4536

EP - 4544

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 12

ER -