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

224 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
DOIs
Publication statusPublished - 1997

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors'. Together they form a unique fingerprint.

  • Cite this

    Calabresi, P., Saiardi, A., Pisani, A., Baik, J. H., Centonze, D., Mercuri, N. B., Bernardi, G., & Borrelli, E. (1997). Abnormal synaptic plasticity in the striatum of mice lacking dopamine D2 receptors. Journal of Neuroscience, 17(12), 4536-4544. https://doi.org/10.1523/jneurosci.17-12-04536.1997