D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade

Neuron. 1997 Nov;19(5):1115-26. doi: 10.1016/s0896-6273(00)80402-x.


Cholinergic interneurons have been implicated in striatally mediated associative learning. In classical conditioning paradigms, conditioned stimuli trigger a transient suppression of neuronal activity that is dependent upon an intact dopaminergic innervation. Our hypothesis was that this suppression reflected dopaminergic enhancement of sensory-linked GABAergic input. As a test, the impact of dopamine on interneuronal GABA(A) receptor function was studied by combined patch-clamp recording and single-cell reverse transcription PCR. Activation of D5 dopamine receptors reversibly enhanced a Zn2+-sensitive component of GABA(A) currents. Although dependent upon protein kinase A (PKA) activation, the modulation was blocked by protein phosphatase 1 (PP1) inhibition, suggesting it was dependent upon dephosphorylation. These results establish a novel mechanism by which intrastriatally released dopamine mediates changes in GABAergic signaling that could underlie the initial stages of associative learning.

Publication types

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

MeSH terms

  • Animals
  • Cholinergic Fibers / metabolism*
  • Corpus Striatum / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Electric Conductivity
  • Enzyme Activation / physiology
  • Interneurons / metabolism
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Protein Phosphatase 1
  • Rats
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D5
  • Receptors, GABA / metabolism
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / physiology*
  • Zinc / pharmacology


  • Drd5 protein, rat
  • Receptors, Dopamine D1
  • Receptors, GABA
  • Receptors, GABA-A
  • Receptors, Dopamine D5
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Zinc