Functional Synaptic Integration of Forebrain GABAergic Precursors into the Adult Spinal Cord
Functional Synaptic Integration of Forebrain GABAergic Precursors into the Adult Spinal Cord
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DOI：
10.1523/jneurosci.2301-16.2016
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发表时间：
2016-11-16
影响因子：
5.3
通讯作者：
Basbaum, Allan I.
中科院分区：
文献类型：
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作者：
Etlin, Alex;Braz, Joao M.;Basbaum, Allan I.
来自内侧神经节隆起（MGE）的胚胎皮层GABA能祖细胞的脊髓移植可以逆转外周神经损伤和紫杉醇诱导的神经性疼痛小鼠模型的机械超敏反应。在这里，我们使用电生理学，免疫组织化学和电子显微镜检查MGE细胞整合到宿主电路和重演内源性抑制电路的程度。无论移植是在神经损伤之前还是之后进行，MGE细胞都发育成成熟的神经元，并表现出皮质和脊髓抑制性中间神经元亚群的特征性放电模式。相反，移植的细胞保留了皮质的形态学和神经化学特性。我们还观察到一个强大的解剖和功能突触整合的移植细胞进入宿主电路在受伤和未受伤的动物。MGE细胞被初级传入神经（包括表达TRPV1的伤害感受器）激活，并在宿主神经元上形成GABA能、荷包牡丹碱敏感的突触。出乎意料的是，在损伤前移植的MGE细胞阻止了机械超敏反应的发展。总之，我们的研究结果提供了一个广泛的，功能性突触整合MGE细胞到宿主脊髓电路的直接确认。这种整合是损伤后背角抑制性张力正常化的基础，可能是损伤前移植的预防作用的原因。
Spinal cord transplants of embryonic cortical GABAergic progenitor cells derived from the medial ganglionic eminence (MGE) can reverse mechanical hypersensitivity in the mouse models of peripheral nerve injury-and paclitaxel-induced neuropathic pain. Here, we used electrophysiology, immunohistochemistry, and electron microscopy to examine the extent to which MGE cells integrate into host circuitry and recapitulate endogenous inhibitory circuits. Whether the transplants were performed before or after nerve injury, the MGE cells developed into mature neurons and exhibited firing patterns characteristic of subpopulations of cortical and spinal cord inhibitory interneurons. Conversely, the transplanted cells preserved cortical morphological and neurochemical properties. We also observed a robust anatomical and functional synaptic integration of the transplanted cells into host circuitry in both injured and uninjured animals. The MGE cells were activated by primary afferents, including TRPV1-expressing nociceptors, and formed GABAergic, bicuculline-sensitive, synapses onto host neurons. Unexpectedly, MGE cells transplanted before injury prevented the development of mechanical hypersensitivity. Together, our findings provide direct confirmation of an extensive, functional synaptic integration of MGE cells into host spinal cord circuits. This integration underlies normalization of the dorsal horn inhibitory tone after injury and may be responsible for the prophylactic effect of preinjury transplants.