Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch

Sensory systems are shaped in postnatal life by the refinement of synaptic connectivity. In the dorsal horn of the spinal cord, somatosensory circuits undergo postnatal activity-dependent reorganisation, including the refinement of primary afferent A-fibre terminals from superficial to deeper spinal dorsal horn laminae which is accompanied by decreases in cutaneous sensitivity. Here we show in the mouse 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 during the initial postnatal period in either sex prevents the normal process of A-fibre refinement and elimination, resulting in altered sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for the 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.