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

TRPV1 receptor mediates glutamatergic synaptic input to dorsolateral periaqueductal gray (dl-PAG) neurons.
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DOI:
10.1152/jn.01023.2006
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发表时间:
2007
影响因子:
2.5
通讯作者:
Jihong Xing;Jianhua Li
Jihong Xing;Jianhua Li
中科院分区:
医学3区
文献类型:
--
作者:
Jihong Xing;Jianhua Li

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本研究的目的是确定瞬时受体电位香草酸1型(TRPV 1)受体在调节神经元活动的背外侧的中脑导水管周围灰质(DL-PAG)通过兴奋性和抑制性突触输入的作用。首先,采用全细胞电压钳记录技术,获得dl-PAG神经元自发性微小兴奋性突触后电流(mEPSC)和抑制性突触后电流(mIPSC)。当将1 μ M辣椒素施加到灌注室中时,mEPSC的频率从3.21 +/- 0.49增加到5.64 +/- 0.64 Hz(P < 0.05,n = 12),而不改变mEPSC的振幅和衰减时间常数。相反,辣椒素对mIPSC没有明显的影响。特异性TRPV 1受体拮抗剂碘树脂毒素(i-RTX,300 nM)将mEPSC的频率从3.51 +/- 0.29降至2.01 +/- 0.2 Hz(P < 0.05,n = 8),但不改变振幅和衰减时间。此外,i-RTX应用于腔室中消除了辣椒素对dl-PAG的mEPSC的影响。在另一个实验中,使用全细胞电流钳方法记录dl-PAG神经元的自发动作电位。辣椒素显著提高了dl-PAG神经元的放电速率,从3.03 +/- 0.38到5.96 +/- 0.87 Hz(n = 8)。在谷氨酸N-甲基-D-天冬氨酸(NMDA)和非NMDA拮抗剂,2-氨基-5-膦酰基戊酸和6-氰基-7-硝基喹喔啉-2,3-二酮的存在下,取消了增加的放电活动。这项研究的结果提供了第一个证据,表明TRPV 1受体的激活通过选择性增强多巴胺能突触输入增加了dl-PAG的神经元活性。
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 periaqueductal gray (dl-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 dl-PAG neurons. As 1 microM 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 dl-PAG. In another experiment, spontaneous action potential of the dl-PAG neurons was recorded using whole cell current-clamp methods. Capsaicin significantly elevated the discharge rate of the dl-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 dl-PAG through selective potentiation of glutamatergic synaptic inputs.