Subtype‐specific effects of dopaminergic D2 receptor activation on synaptic trains in layer V pyramidal neurons in the mouse prefrontal cortex

In humans, prefrontal cortical areas are known to support executive functions. In mice, these functions are mediated by homologous regions in the medial prefrontal cortex (mPFC). Executive processes are critically dependent on optimal levels of dopamine (DA), but the cellular mechanisms of DA modulation are incompletely understood. Stable patterns of neuronal activity may be sensitive to frequency‐dependent changes in synaptic transmission. We characterized the effects of D2 receptor (D2R) activation on short‐term excitatory postsynaptic potential (EPSP) dynamics evoked at varying frequencies in the two subtypes of layer V pyramidal neurons in mouse mPFC. We isolated NMDA receptor and non‐NMDA receptor‐mediated components of EPSP trains evoked by stimulating fibers within layer V or layer I. All significant effects of D2 receptor activation were confined to type I (corticopontine) cells. First, we found that with layer I stimulation, D2R activation reduces the amplitude of NMDAR‐mediated EPSPs, with no effect on facilitation or depression of these responses at lower frequencies, but leading to facilitation with high frequency stimulation. Further, the non‐NMDA component also underwent synaptic depression at low frequencies. Second, with layer V stimulation, D2R activation had no effect on NMDA or non‐NMDA receptor‐mediated EPSP components. Overall, our results suggest that D2R activation may modulate memory functions by inhibiting ‘top‐down’ influences from apical tuft inputs activated at low frequencies, while promoting ‘top‐down’ influences from inputs activated at higher frequencies. These data provide further insight into mechanisms of dopamine's modulation of executive functions.