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

Xu, Yajing; Koch, Stephanie C; Chamessian, Alexander; He, Qianru; Sundukova, Mayya; Heppenstall, Paul; Ji, RuRong; ... Beggs, Simon; + view all (2024) Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch. Journal of Neuroscience , 44 (2) , Article e1354232023. 10.1523/JNEUROSCI.1354-23.2023. Green open access

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Abstract

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 reorganization, including the refinement of primary afferent A-fiber 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-fiber 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-fiber refinement and elimination, resulting in an altered sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioral 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-fiber projections remain in the dorsal horn, and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch.

Type: Article
Title: Microglial Refinement of A-Fiber Projections in the Postnatal Spinal Cord Dorsal Horn Is Required for Normal Maturation of Dynamic Touch
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.1354-23.2023
Publisher version: http://dx.doi.org/10.1523/jneurosci.1354-23.2023
Language: English
Additional information: Copyright © 2023 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Development; microglia; postnatal; somatosensory; spinal; touch
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10185909
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