Distinct roles of D1 and D5 dopamine receptors in motor activity and striatal synaptic plasticity

Diego Centonze, Cristina Grande, Emilia Saulle, Ana B. Martín, Paolo Gubellini, Nancy Pavón, Antonio Pisani, Giorgio Bernardi, Rosario Moratalla, Paolo Calabresi

Research output: Contribution to journalArticle

Abstract

Stimulation of dopamine (DA) receptors in the striatum is essential for voluntary motor activity and for the generation of plasticity at corticostriatal synapses. In the present study, mice lacking DA D1 receptors have been used to investigate the involvement of the D 1-like class (D1 and D5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D1 and D5 receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D1 receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D5 receptors prevented LTD. On the other side, genetic ablation of D1 receptors increased locomotor activity, whereas the D 1/D5 receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D1 receptors. Endogenous DA stimulated D1 and D5 receptors in distinct subtypes of striatal neurons to induce, respectively, LTP and LTD. In control mice, in fact, LTP was blocked by inhibiting the D1-protein kinase A pathway in the recorded spiny neuron, whereas the striatal nitric oxide-producing interneuron was presumably the neuronal subtype stimulated by D5 receptors during the induction phase of LTD. Understanding the role of DA receptors in striatal function is essential to gain insights into the neural bases of critical brain functions and of dramatic pathological conditions such as Parkinson's disease, schizophrenia, and drug addiction.

Original languageEnglish
Pages (from-to)8506-8512
Number of pages7
JournalJournal of Neuroscience
Volume23
Issue number24
Publication statusPublished - Sep 17 2003

Keywords

  • Basal ganglia
  • Behavior
  • In vitro electrophysiology
  • Interneurons
  • Long-term depression
  • Long-term potentiation
  • Nitric oxide

ASJC Scopus subject areas

  • Neuroscience(all)

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