Platelet-derived growth factor (PDGF)-BB inhibits AMPA receptor-mediated synaptic transmission via PDGF receptor-β in murine nucleus tractus solitarius

Abstract

Although platelet-derived growth factor (PDGF)-BB activates PDGF receptor-β (PDGFR-β) and, in turn, inhibits the glutamate N-methyl- d-aspartate (NMDA) receptor function, whether PDGF-BB modulates the CNS function mediated by another glutamate receptors, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, remains poorly understood. Here we now report the inhibitory effect of PDGF-BB on the AMPA receptor function in the nucleus tractus solitarius (NTS) by using slice patch-clamp techniques. Excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of the tractus solitarius in mouse NTS second-order neurons. EPSCs were nearly completely eliminated by CNQX but not by MK-801, implying mediation through non-NMDA receptors. PDGF-BB significantly decreased the amplitude of EPSCs without affecting the mean decay time constant. This inhibitory effect was transient and reversible after removing PDGF-BB. Furthermore, PDGF-BB significantly reduced the amplitude of AMPA-induced currents in NTS neurons, which showed that PDGF-BB could suppress the AMPA receptor-mediated excitatory input via the postsynaptic mechanism. The inhibitory effect of PDGF-BB on EPSCs was not observed in mutant mice with conditional deletion of the PDGFR-β gene in neurons. Together, these studies suggest that the PDGF-B/PDGFR-β axis inhibits the AMPA receptor-mediated synaptic transmission that comprises the major part of the primary afferent to the NTS second-order neuron. The detected inhibitory action may be involved in the CNS regulation of the respiratory response.