Dopamine D1/D5 receptor modulation of excitatory synaptic inputs to layer V prefrontal cortex neurons

Dopamine acts mainly through the D1/D5 receptor in the prefrontal cortex (PFC) to modulate neural activity and behaviors associated with working memory. To understand the mechanism of this effect, we examined the modulation of excitatory synaptic inputs onto layer V PFC pyramidal neurons by D1/D5 receptor stimulation. D1/D5 agonists increased the size of N-methyl-d-aspartate (NMDA) component of excitatory postsynaptic currents (EPSCs) through a postsynaptic mechanism. In contrast, D1/D5 agonists caused a slight reduction in the size of the non-NMDA component of EPSCs through a small decrease in release probability. With 20 Hz synaptic trains, we found that the D1/D5 agonists increased depolarization of summating the NMDA component of excitatory postsynaptic potential (EPSP). By increasing the NMDA component of EPSCs, yet slightly reducing release, D1/D5 receptor activation selectively enhanced sustained synaptic inputs and equalized the sizes of EPSPs in a 20-Hz train.