Abstract

Previous research demonstrated that dopamine produces concentration-dependent changes in synaptic transmission in the entorhinal cortex, wherein high concentrations of dopamine (50 µM) suppress evoked excitatory postsynaptic potentials (EPSPs) and lower concentrations of dopamine (1 to 10 µM) facilitate them. Whole-cell current clamp recordings were used to investigate the dopaminergic facilitation of synaptic responses in layer II neurons of the lateral entorhinal cortex. Surprisingly, the pattern of changes in EPSPs was dependent on cell type. During bath applications of 1 µM dopamine, fan cells showed a facilitation of the amplitude of EPSPs evoked by layer I stimulation. In contrast, pyramidal cells showed mixed modulation of EPSPs in response to dopamine, with different cells showing either facilitation or suppression effects. Voltage clamp recordings of excitatory postsynaptic currents suggest that dopamine facilitates AMPA glutamate receptor-mediated EPSCs. To determine the dopaminegic receptor subtype involved, either the D1 receptor blocker SCH23390 (50 µM) or the D2 receptor blocker sulpiride (50 µM) was bath applied to the slices prior to dopamine. Application of SCH 23390 blocked the facilitation of EPSCs, whereas application of sulpiride had no significant effect. Therefore, the dopaminergic enhancement of EPSCs is likely to be mediated primarily through D1-like receptors. D1 receptors can act through a variety of intracellular signaling pathways to modulate synaptic strength. The role of signaling via protein kinase A was tested by including the PKA inhibitor H-89 in the recording pipette solution. Cells filled with H-89 did not show a facilitation of EPSCs in response to dopamine application. Thus, the dopamine-induced facilitation of AMPA receptor-mediated synaptic responses in the lateral entorhinal cortex appears to be mediated via a D1 receptor-dependent increase in PKA activity.