Microglial refinement of A-fibre projections in the postnatal spinal cord dorsal horn is required for normal maturation of dynamic touch
Microglial refinement of A-fibre projections in the postnatal spinal cord dorsal horn is required for normal maturation of dynamic touch
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DOI：
10.1101/2021.03.22.436389
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发表时间：
2022-05
期刊：
影响因子：
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通讯作者：
Yajing Xu;S. Koch;Alexander G Chamessian;Qianru He;M. Sundukova;P. Heppenstall;Ru-Rong Ji;M. Fitzgerald;S. Beggs
中科院分区：
文献类型：
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作者：
Yajing Xu;S. Koch;Alexander G Chamessian;Qianru He;M. Sundukova;P. Heppenstall;Ru-Rong Ji;M. Fitzgerald;S. Beggs
感觉系统在出生后的生命中通过突触连接的完善而形成。在脊髓的背角，感觉回路经历出生后活动依赖性重组，包括初级传入A纤维从浅层到深层的回缩，这伴随着皮肤敏感性的降低。在这里，我们表明，小胶质细胞，在中枢神经系统的居民免疫细胞，吞噬A-纤维终端在浅层在第一周的生活。此时小胶质细胞吞噬的遗传扰动阻止了A纤维收缩的正常过程，导致背角细胞对动态触觉皮肤刺激的敏感性增加，以及对动态触觉的行为超敏反应。因此，功能性小胶质细胞是必要的正常出生后发育的背角感觉回路。在没有小胶质细胞吞噬的情况下，多余的A纤维投射留在背角中，感觉连接的平衡被破坏，导致终身对动态触摸超敏反应。影响声明小胶质细胞在正常发育期间吞噬浅层脊髓背角中多余的A纤维，其破坏导致长期异常的动态触摸处理和行为。
Sensory systems are shaped in postnatal life by the refinement of synaptic connections. In the dorsal horn of the spinal cord, sensory circuits undergo postnatal activity dependent reorganisation, including the retraction of primary afferent A-fibres from superficial to deeper laminae which is accompanied by decreases in cutaneous sensitivity. Here we show that microglia, the resident immune cells in the CNS, phagocytose A-fibre terminals in superficial laminae in the first weeks of life. Genetic perturbation of microglial engulfment at that time prevents the normal process of A-fibre retraction, resulting in increased sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for normal postnatal development of dorsal horn sensory circuits. In the absence of microglial engulfment, superfluous A-fibre projections remain in the dorsal horn and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch. Impact statement Microglia phagocytose superfluous A-fibres in the superficial spinal dorsal horn during normal development, the disruption of which leads to long term aberrant dynamic touch processing and behaviour.