Prostaglandin E 2 (PGE 2) inhibits glutamatergic synaptic transmission in dorsolateral periaqueductal gray (dl-PAG)

Abstract

The purpose of this study was to determine the role of prostaglandin E 2 (PGE 2) 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 PGE 2 significantly decreased the frequency of miniature EPSCs and amplitude of evoked EPSCs. The effects were mimicked by sulprostone, an agonist to PGE 2 EP 3 receptors. In contrast, PGE 2 had no distinct effect on IPSCs. In addition, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. PGE 2 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 PGE 2 inhibits the neuronal activity of the dl-PAG via selective attenuation of glutamatergic synaptic inputs, likely due to the activation of presynaptic EP 3 receptors.