Postsynaptic modulation of AMPA- and NMDA-receptor currents by Group III metabotropic glutamate receptors in rat nucleus accumbens

Abstract

Whole cell patch clamp recordings from rat nucleus accumbens neurons were made in order to study the effect of metabotropic glutamate receptors and dopamine on postsynaptic glutamate receptor mediated currents. AMPA- and NMDA-R currents were evoked by flash photolysis of caged glutamate, while spike-dependent release of neurotransmitters was prevented by adding tetrodotoxin and bicuculline to the bath solution. Spontaneous potentiation of NMDA- but not AMPA-R current was observed in the early phase of stimulation, followed by depotentiation and subsequent stabilization. The Group III metabotropic glutamate receptor antagonist MAP4 induced a transient potentiation of both AMPA- and NMDA-R current amplitudes, without affecting rise times and decay time constants. In contrast, the Group I–II metabotropic glutamate receptor antagonist MCPG and the neurotransmitter dopamine did not exert significant effects on either AMPA- or NMDA-R currents. These data suggest that at least one of the Group III subtypes is located postsynaptically in the nucleus accumbens and is able to dampen the activity of ionotropic glutamatergic receptors. In contrast, our results do not support a modulation of postsynaptic AMPA- and NMDA-R currents by Group I/II metabotropic glutamate receptors or dopamine. Modulation of both AMPA- and NMDA-R currents in the nucleus accumbens is likely to play a major role in setting the cellular excitability in response to behaviourally relevant limbic inputs, and in regulating the plasticity of these responses.