Regional Heterogeneity of D2-Receptor Signaling in the Dorsal Striatum and Nucleus Accumbens

Neuron. 2018 May 2;98(3):575-587.e4. doi: 10.1016/j.neuron.2018.03.038. Epub 2018 Apr 12.

Abstract

Dopamine input to the dorsal and ventral striatum originates from separate populations of midbrain neurons. Despite differences in afferent inputs and behavioral output, little is known about how dopamine release is encoded by dopamine receptors on medium spiny neurons (MSNs) across striatal subregions. Here we examined the activation of D2 receptors following the synaptic release of dopamine in the dorsal striatum (DStr) and nucleus accumbens (NAc) shell. We found that D2 receptor-mediated synaptic currents were slower in the NAc and this difference occurred at the level of D2-receptor signaling. As a result of preferential coupling to Gαo, we also found that D2 receptors in MSNs demonstrated higher sensitivity for dopamine in the NAc. The higher sensitivity in the NAc was eliminated following cocaine exposure. These results identify differences in the sensitivity and timing of D2-receptor signaling across the striatum that influence how nigrostriatal and mesolimbic signals are encoded across these circuits.

Keywords: GPCR; addiction; basal ganglia; dopamine; metabotropic; schizophrenia; sensitization; striatum; synaptic transmission.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Receptors, Dopamine D2
  • Dopamine