Dopamine enhances EPSCs in layer II-III pyramidal neurons in rat prefrontal cortex.
Dopaminergic inputs to the prefrontal cortex (PFC) are important for the integration of neuronal signals, the formation of working memory, and the establishment of memory fields. A detailed characterization of cellular mechanisms underlying the effects of dopamine on PFC is still emerging. We have examined how dopamine affects excitatory synaptic transmission in the PFC using whole-cell patch-clamp recording from visually identified layer II-III pyramidal cells in vitro. Bath application of dopamine significantly enhanced EPSC amplitudes. Pharmacologically isolated AMPA and NMDA receptor-mediated EPSCs were increased to a similar extent. Application of the specific D1-like receptor agonist SKF38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrobromide] significantly increased EPSC amplitude, whereas the D2-like receptor agonist quinpirole had no effect. Responses to pressure-applied glutamate were also enhanced by dopamine, indicating a postsynaptic mechanism. Inclusion of the Ca(2+) chelator BAPTA in the recording pipette blocked the dopamine enhancement. When the PKA inhibitory peptide PKI [5-24] was included in the recording pipette, dopamine did not affect EPSCs. Similarly, when the Ca(2+)/calmodulin-kinase II (CaMKII) inhibitory peptide was present in the pipette, dopamine enhancement of EPSCs was not observed in any of the cells tested. These results indicate that EPSC enhancement may be attributable to a postsynaptic signaling cascade involving Ca(2+), PKA, and CaMKII.
Gonzalez-Islas
Carlos
C
Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Hablitz
John J
JJ
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002614:Chelating Agents / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D002614:Chelating Agents; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004533:Egtazic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C013411:biocytin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D008239:Lysine; D004298:Dopamine