The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, < 10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 x 50 Hz) induced a homosynaptic PTP (decayed: approximately 1 min). The D1-like antagonist SCH23390 (1 microm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting approximately 4 min, but only at 2x intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V-->V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting approximately 6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V-->V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III-->V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing.