Optogenetic Evidence for a Direct Circuit Linking Nociceptive Transmission through the Parabrachial Complex with Pain-Modulating Neurons of the Rostral Ventromedial Medulla (RVM).
Optogenetic Evidence for a Direct Circuit Linking Nociceptive Transmission through the Parabrachial Complex with Pain-Modulating Neurons of the Rostral Ventromedial Medulla (RVM).
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DOI：
10.1523/eneuro.0202-17.2017
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发表时间：
2017-05
期刊：
影响因子：
3.4
通讯作者：
Heinricher MM
中科院分区：
文献类型：
--
作者：
Chen Q;Roeder Z;Li MH;Zhang Y;Ingram SL;Heinricher MM
臂旁复合体（PB）是一种功能和解剖学上复杂的结构，涉及一系列稳态和感觉功能，包括伤害性传递。也有证据表明，PB可以参与下行疼痛调节系统，其中最好的特点是头端腹内侧延髓（RVM）。RVM神经元的两个不同的类别，“ON-细胞”和“OFF-细胞”，分别发挥净原伤害感受和抗伤害感受作用。PB最近被证明是RVM ON-和OFF-细胞的伤害性信息的中继。本实验在轻度麻醉的大鼠和成年RVM切片中使用光遗传学方法来确定是否存在来自PB的对RVM疼痛调节神经元的直接的、功能相关的输入。全细胞膜片钳记录表明，PB传递直接的多巴胺能和GABA能输入到RVM神经元。与此一致，在体内记录显示，ON-和OFF-细胞的伤害性诱发的反应被RVM中表达古视紫红质（ArchT）的PB末端的光遗传学失活抑制，表明OFF-细胞的净抑制性输入和ON-细胞的净兴奋性输入被急性伤害性刺激所参与。此外，大多数ON-和OFF-细胞响应于RVM中通道视紫红质（ChR 2）表达末端的光遗传学激活，证实了PB对RVM疼痛调节神经元的直接影响。这些数据表明，在基础条件下，从PB到RVM的直接连接将伤害性信息传递给RVM的疼痛调节神经元。它们还揭示了PB的额外输入，具有激活两类RVM疼痛调节神经元的能力，以及在不同生理和病理生理条件下被招募的潜力。
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, in vivo 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.