Purinergic signaling between neurons and satellite glial cells of mouse dorsal root ganglia modulates neuronal excitability in vivo.
Purinergic signaling between neurons and satellite glial cells of mouse dorsal root ganglia modulates neuronal excitability in vivo.
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DOI：
10.1097/j.pain.0000000000002556
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发表时间：
2022-08-01
期刊：
影响因子：
7.4
通讯作者：
中科院分区：
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背根神经节（DRG）内的初级感觉神经元被卫星胶质细胞（SGCs）包裹，神经元与SGCs的相互作用可能影响躯体感觉，尤其是伤害性感觉的传递。P2嘌呤能受体（P2 Rs）是DRG神经元与SGCs之间双向相互作用的关键元件。然而，由于细胞类型是如此接近，常规的方法，如体外培养和电生理记录是不足以调查这些细胞在群体水平的生理相关的反应。在这里，我们进行了体内钙成像，以调查Pirt-GCaMP 6s小鼠中数百个DRG神经元的激活，并原位评估GFAP-GCaMP 6s小鼠中的SGC激活。本研究采用药理学和电生理学相结合的方法，在群体水平上研究了α，β-MeATP（α，β-methyleneadenosine 5′-triphosphate，α，β-MeATP）介导的神经节嘌呤能信号对神经元活动和兴奋性的调节作用。我们发现，α，β-MeATP通过激活P2 X3 R诱导小神经元（可能是伤害感受器）的强烈激活。大的神经元，可能是非伤害性的，也被α，β-MeATP激活，但有延迟。阻断泛连接蛋白1通道减弱了DRG神经元的晚期反应，表明P2 R刺激可能随后诱导旁分泌ATP释放，这可能进一步激活神经节中的细胞。此外，神经节α，β-MeATP治疗在体内致敏小神经元，并增强脊髓宽动态范围神经元对随后的C-纤维输入的反应，表明通过神经节P2 R信号转导的调制可以显著影响伤害性神经元的兴奋性和疼痛传递。因此，靶向神经节内的功能性P2 R可能代表疼痛调节的重要新策略。
Primary sensory neurons in dorsal root ganglia (DRG) are wrapped by satellite glial cells (SGCs), and neuron-SGC interaction may affect somatosensation, especially nociceptive transmission. P2-purinergic receptors (P2Rs) are key elements in the two-way interactions between DRG neurons and SGCs. However, because the cell types are in such close proximity, conventional approaches such as in vitro culture and electrophysiologic recordings are not adequate to investigate the physiologically relevant responses of these cells at a population level. Here, we performed in vivo calcium imaging to survey the activation of hundreds of DRG neurons in Pirt-GCaMP6s mice and to assess SGC activation in GFAP-GCaMP6s mice in situ. By combining pharmacologic and electrophysiologic techniques, we investigated how ganglionic purinergic signaling initiated by α,β-methyleneadenosine 5′-triphosphate (α,β-MeATP) modulates neuronal activity and excitability at a population level. We found that α,β-MeATP induced robust activation of small neurons—likely nociceptors—through activation of P2X3R. Large neurons, which are likely non-nociceptive, were also activated by α,β-MeATP, but with a delay. Blocking pannexin 1 channels attenuated the late phase response of DRG neurons, indicating that P2R stimulation may subsequently induce paracrine ATP release, which could further activate cells in the ganglion. Moreover, ganglionic α,β-MeATP treatment in vivo sensitized small neurons and enhanced responses of spinal wide-dynamic-range neurons to subsequent C-fiber inputs, suggesting that modulation via ganglionic P2R signaling could significantly affect nociceptive neuron excitability and pain transmission. Therefore, targeting functional P2Rs within ganglia may represent an important new strategy for pain modulation.
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影响因子：
4.7
作者：
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通讯作者：
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DOI：
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发表时间：
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期刊：
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