Postsynaptic dopamine D3 receptor modulation of evoked IPSCs via GABA(A) receptor endocytosis in rat hippocampus

Dopamine is known to be an important modulator of learning and memory processes, but its mechanisms of action at the cellular level are diverse and are not fully characterized. In the hippocampus, pharmacologically isolated monosynaptic IPSCs were measured using the whole-cell voltage-clamp recording technique. Both electrically evoked and spontaneous miniature GABA(A) receptor currents were recorded from CA1 pyramidal neurons in slices obtained from mature rats in the presence of the D3-selective agonist PD128907. The activation of D3 receptors inhibited synaptic GABAergic input without affecting presynaptic function or passive membrane properties. Inhibition of IPSCs evoked from stratum radiatum occurred via regulation of dynamin-dependent trafficking of the GABA(A) receptor, as inclusion of dynamin inhibitory peptide (50 microM) in the recording solution prevented the inhibitory effects of PD128907 (1 microM). This effect of D3 receptor activation could be prevented by intracellular application of either an inhibitor of protein kinase A (PKI, 20 microM) or an activator of protein kinase A (8-OH-cAMP, 50 microM). Neither synchronous IPSCs evoked from the stratum oriens nor asynchronous miniature IPSCs recorded from the stratum radiatum were affected by D3 agonist. The induction of long-term potentiation (LTP) of the extracellular field response in both the stratum radiatum and stratum oriens demonstrated that only potentiation in the stratum radiatum was significantly enhanced by PD128907 (1 microM). Our results suggest that the activation of D3 receptors can modulate GABA(A) receptor endocytosis in the hippocampus in a lamina specific manner, and thereby alter the efficacy of GABAergic transmission in the stratum radiatum of the CA1 region through a postsynaptic mechanism of action.