Department of Neurological Surgery, Oregon Health & Science University, Portland, OR 97239.
Neuroscience Graduate Program, Oregon Health & Science University, Portland, OR 97239.
eNeuro. 2017 Jun 26;4(3). doi: 10.1523/ENEURO.0202-17.2017. eCollection 2017 May-Jun.
The parabrachial complex (PB) is a functionally and anatomically complex structure involved in a range of homeostatic and sensory functions, including nociceptive transmission. There is also evidence that PB can engage descending pain-modulating systems, the best characterized of which is the rostral ventromedial medulla (RVM). Two distinct classes of RVM neurons, "ON-cells" and "OFF-cells," exert net pronociceptive and anti-nociceptive effects, respectively. PB was recently shown to be a relay of nociceptive information to RVM ON- and OFF-cells. The present experiments used optogenetic methods in a lightly anesthetized rat and an adult RVM slice to determine whether there are direct, functionally relevant inputs to RVM pain-modulating neurons from PB. Whole-cell patch-clamp recordings demonstrated that PB conveys direct glutamatergic and GABAergic inputs to RVM neurons. Consistent with this, recording showed that nociceptive-evoked responses of ON- and OFF-cells were suppressed by optogenetic inactivation of archaerhodopsin (ArchT)-expressing PB terminals in RVM, demonstrating that a net inhibitory input to OFF-cells and net excitatory input to ON-cells are engaged by acute noxious stimulation. Further, the majority of ON- and OFF-cells responded to optogenetic activation of channelrhodopsin (ChR2)-expressing terminals in the RVM, confirming a direct PB influence on RVM pain-modulating neurons. These data show that a direct connection from the PB to the RVM conveys nociceptive information to the pain-modulating neurons of RVM under basal conditions. They also reveal additional inputs from PB with the capacity to activate both classes of RVM pain-modulating neurons and the potential to be recruited under different physiological and pathophysiological conditions.
脑桥臂旁复合体（PB）是一个功能和解剖结构复杂的结构，参与了一系列的稳态和感觉功能，包括伤害性感受的传递。也有证据表明，PB 可以参与下行痛觉调制系统，其中最具特征的是延髓头端腹内侧区（RVM）。RVM 中有两种不同类型的神经元，“ON 细胞”和“OFF 细胞”，分别发挥着净致痛和抗痛的作用。最近的研究表明，PB 是伤害性感受信息传递到 RVM ON 和 OFF 细胞的中继站。本实验采用光遗传学方法在轻度麻醉大鼠和成年 RVM 切片中，确定 PB 是否有直接的、功能相关的传入纤维投射到 RVM 的痛觉调制神经元。全细胞膜片钳记录显示，PB 向 RVM 神经元传递直接的谷氨酸能和 GABA 能传入。与之一致的是，在 RVM 中，通过光遗传失活表达 archerhodopsin（ArchT）的 PB 末梢，ON 和 OFF 细胞的伤害性感受诱发反应被抑制，表明急性伤害性刺激引起 OFF 细胞的净抑制性传入和 ON 细胞的净兴奋性传入。此外，大多数 ON 和 OFF 细胞对 RVM 中表达 channelrhodopsin（ChR2）的末梢的光遗传激活有反应，证实了 PB 对 RVM 痛觉调制神经元的直接影响。这些数据表明，PB 与 RVM 之间的直接连接在基础条件下将伤害性感受信息传递到 RVM 的痛觉调制神经元。它们还揭示了来自 PB 的额外输入，这些输入有能力激活 RVM 中这两类痛觉调制神经元，并有可能在不同的生理和病理生理条件下被募集。
