Prostaglandin E2 (PGE2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

The purpose of this study was to determine the role of prostaglandin E2 (PGE2) in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs) of the dl-PAG neurons. Our results show that PGE2 significantly decreased the frequency of miniature EPSCs and amplitude of evoked EPSCs. The effects were mimicked by sulprostone, an agonist to PGE2 EP3 receptors. In contrast, PGE2 had no distinct effect on IPSCs. In addition, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. PGE2 significantly attenuated the discharge rate of the dl-PAG neurons. The decreased firing activity was abolished in the presence of glutamate NMDA and non-NMDA receptor antagonists. The results from the current study provide the first evidence indicating that PGE2 inhibits the neuronal activity of the dl-PAG via selective attenuation of glutamatergic synaptic inputs, likely due to the activation of presynaptic EP3 receptors.