TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons

The purpose of this study was to determine the role of transient receptor potential vanilloid type 1 ( TRPV1) receptor in modulating neuronal activity of the dorsolateral periaque-ductal gray ( d1-PAG) through excitatory and inhibitory synaptic inputs. First, whole cell voltage-clamp recording was performed to obtain the spontaneous miniature excitatory postsynaptic currents ( mEPSCs) and inhibitory postsynaptic currents ( mIPSCs) of the d1- PAG neurons. As 1 mu M of capsaicin was applied into the perfusion chamber, the frequency of mEPSCs was increased from 3.21 +/- 0.49 to 5.64 +/- 0.64 Hz ( P < 0.05, n = 12) without altering the amplitude and the decay time constant of mEPSCs. In contrast, capsaicin had no distinct effect on mIPSCs. A specific TRPV1 receptor antagonist, iodo-resiniferatoxin ( i- RTX, 300 nM), decreased the frequency of mEPSCs from 3.51 +/- 0.29 to 2.01 +/- 0.2 Hz ( P < 0.05, n = 8) but did not alter the amplitude and decay time. In addition, i- RTX applied into the chamber abolished the effect of capsaicin on mEPSC of the d1-PAG. In another experiment, spontaneous action potential of the d1- PAG neurons was recorded using whole cell current- clamp methods. Capsaicin significantly elevated the discharge rate of the d1- PAG neurons from 3.03 +/- 0.38 to 5.96 +/- 0.87 Hz ( n = 8). The increased firing activity was abolished in the presence of glutamate N-methy-D- aspartate ( NMDA) and non- NMDA antagonists, 2-amino-5-phosphonopentanoic acid, and 6-cyano-7-nitroquinoxaline-2,3-dione. The results from this study provide the first evidence indicating that activation of TRPV1 receptors increases the neuronal activity of the d1- PAG through selective potentiation of glutamatergic synaptic inputs.