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bioRxiv · 10.1101/2021.03.22.436389

Microglial refinement of spinal cord sensory circuitry regulates normal maturation of dynamic touch.

Xu, Y.·Koch, S.·Chamessian, A.·He, Q.·Sundukova, M.·Heppenstall, P.·Ji, R. R.·Fitzgerald, M.·Beggs, S.
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Abstract

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 statementMicroglia 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.

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Xu, Y., Koch, S., Chamessian, A., He, Q., Sundukova, M., Heppenstall, P., Ji, R. R., Fitzgerald, M., Beggs, S.. 2021-03-22. Microglial refinement of spinal cord sensory circuitry regulates normal maturation of dynamic touch.. https://doi.org/10.1101/2021.03.22.436389

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