D5 dopamine receptors enhance Zn2+-sensitive GABA(A) currents in striatal cholinergic interneurons through a PKA/PP1 cascade.
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.
Yan
Z
Z
Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163, USA.
Surmeier
D J
DJ
D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004553:Electric Conductivity; D004789:Enzyme Activation / Q000502:physiology; D007395:Interneurons / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D054645:Protein Phosphatase 1; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D018079:Receptors, GABA / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology
C493607:Drd5 protein, rat; D017447:Receptors, Dopamine D1; D018079:Receptors, GABA; D011963:Receptors, GABA-A; D050641:Receptors, Dopamine D5; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D015032:Zinc