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.