Carvalho Gil B, Mulpuri Yatendra, Damasio Antonio, Spigelman Igor
Brain and Creativity Institute, University of Southern California, 3620 A McClintock Avenue, Suite 265, Los Angeles 90089-2921, CA, USA.
Division of Oral Biology & Medicine, School of Dentistry, University of California, 10833 Le Conte Avenue, 63-078 CHS, Los Angeles 090095-1668, CA, USA.
Neuroscience. 2019 Dec 15;423:98-108. doi: 10.1016/j.neuroscience.2019.09.038. Epub 2019 Nov 2.
Non-synaptic transmission is pervasive throughout the nervous system. It appears especially prevalent in peripheral ganglia, where non-synaptic interactions between neighboring cell bodies have been described in both physiological and pathological conditions, a phenomenon referred to as cross-depolarization (CD) and thought to play a role in sensory processing and chronic pain. CD has been proposed to be mediated by a chemical agent, but its identity has remained elusive. Here, we report that in the rat dorsal root ganglion (DRG), the P2Y1 purinergic receptor (P2RY1) plays an important role in regulating CD. The effect of P2RY1 is cell-type specific: pharmacological blockade of P2RY1 inhibited CD in A-type neurons while enhancing it in C-type neurons. In the nodose ganglion of the vagus, CD requires extracellular calcium in a large percentage of cells. In contrast, we show that in the DRG extracellular calcium appears to play no major role, pointing to a mechanistic difference between the two peripheral ganglia. Furthermore, we show that DRG glial cells also play a cell-type specific role in CD regulation. Fluorocitrate-induced glial inactivation had no effect on A-cells but enhanced CD in C-cells. These findings shed light on the mechanism of CD in the DRG and pave the way for further analysis of non-synaptic neuronal communication in sensory ganglia.
非突触传递在整个神经系统中普遍存在。它在周围神经节中似乎尤为常见，在生理和病理条件下，相邻细胞体之间的非突触相互作用已被描述，这种现象被称为交叉去极化（CD），并被认为在感觉处理和慢性疼痛中起作用。有人提出CD是由一种化学物质介导的，但其身份一直难以确定。在这里，我们报告在大鼠背根神经节（DRG）中，P2Y1嘌呤能受体（P2RY1）在调节CD中起重要作用。P2RY1的作用具有细胞类型特异性：对P2RY1的药理阻断抑制了A型神经元中的CD，同时增强了C型神经元中的CD。在迷走神经的结状神经节中，很大一部分细胞中的CD需要细胞外钙。相比之下，我们发现在DRG中细胞外钙似乎不起主要作用，这表明两个周围神经节之间存在机制差异。此外，我们表明DRG神经胶质细胞在CD调节中也发挥细胞类型特异性作用。氟柠檬酸诱导的神经胶质细胞失活对A细胞没有影响，但增强了C细胞中的CD。这些发现揭示了DRG中CD的机制，并为进一步分析感觉神经节中的非突触神经元通讯铺平了道路。
