Dopamine D1 receptor activation regulates sodium channel‐dependent EPSP amplification in rat prefrontal cortex pyramidal neurons

Dopamine (DA) effects on prefrontal cortex (PFC) neurons are essential for the cognitive functions mediated by this cortical area. However, the cellular mechanisms of DA neuromodulation in neocortex are not well understood. We characterized the effects of D1‐type DA receptor (D1R) activation on the amplification (increase in duration and area) of excitatory postsynaptic potentials (EPSPs) at depolarized potentials, in layer 5 pyramidal neurons from rat PFC. Simulated EPSPs (sEPSPs) were elicited by current injection, to determine the effects of D1R activation independent of modulation of transmitter release or glutamate receptor currents. Application of the D1R agonist SKF81297 attenuated sEPSP amplification at depolarized potentials in a concentration‐dependent manner. The SKF81297 effects were inhibited by the D1R antagonist SCH23390. The voltage‐gated Na+ channel blocker tetrodotoxin (TTX) abolished the effects of SKF81297 on sEPSP amplification, suggesting that Na+ currents are necessary for the D1R effect. Furthermore, blockade of 4‐AP‐ and TEA‐sensitive K+ channels in the presence of TTX significantly increased EPSP amplification, arguing against the possibility that SKF81297 up‐regulates currents that attenuate sEPSP amplification. SKF81297 application attenuated the subthreshold response to injection of depolarizing current ramps, in a manner consistent with a decrease in the persistent Na+ current. In addition, D1R activation decreased the effectiveness of temporal EPSP summation during 20 Hz sEPSP trains, selectively at depolarized membrane potentials. Therefore, the effects of D1R activation on Na+ channel‐dependent EPSP amplification may regulate the impact of coincidence detection versus temporal integration mechanisms in PFC pyramidal neurons.

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