Dopamine Modulation of Excitatory Currents in the Striatum Is Dictated by the Expression of D1 or D2 Receptors and Modified by Endocannabinoids

Eur J Neurosci. 2010 Jan;31(1):14-28. doi: 10.1111/j.1460-9568.2009.07047.x. Epub 2009 Dec 21.

Abstract

Striatal medium-sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter gene to identify MSSNs containing D1 or D2 receptor subtypes were used to examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices and postsynaptic N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents in acutely isolated cells. The results demonstrated dopamine receptor-specific modulation of sEPSCs. Dopamine and D1 agonists increased sEPSC frequency in D1 receptor-expressing MSSNs (D1 cells), whereas dopamine and D2 agonists decreased sEPSC frequency in D2 receptor-expressing MSSNs (D2 cells). These effects were fully (D1 cells) or partially (D2 cells) mediated through retrograde signaling via endocannabinoids. A cannabinoid 1 receptor (CB1R) agonist and a blocker of anandamide transporter prevented the D1 receptor-mediated increase in sEPSC frequency in D1 cells, whereas a CB1R antagonist partially blocked the decrease in sEPSC frequency in D2 cells. At the postsynaptic level, low concentrations of a D1 receptor agonist consistently increased NMDA and AMPA currents in acutely isolated D1 cells, whereas a D2 receptor agonist decreased these currents in acutely isolated D2 cells. These results show that both glutamate release and postsynaptic excitatory currents are regulated in opposite directions by activation of D1 or D2 receptors. The direction of this regulation is also specific to D1 and D2 cells. We suggest that activation of postsynaptic dopamine receptors controls endocannabinoid mobilization, acting on presynaptic CB1Rs, thus modulating glutamate release differently in glutamate terminals projecting to D1 and D2 cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cannabinoid Receptor Modulators / metabolism*
  • Cells, Cultured
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Dopamine / metabolism*
  • Endocannabinoids*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Glutamic Acid / metabolism
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • N-Methylaspartate / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / metabolism*
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism*
  • Signal Transduction
  • Synapses / drug effects
  • Synapses / physiology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism

Substances

  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Glutamic Acid
  • N-Methylaspartate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Dopamine