Spinal Cord Microglia in the Development of Touch

Adaptive interactions with environmental stressors are crucial to survival and are heavily reliant on detection and perception of somatosensory modalities such as noxious and innocuous touch, pressure, itch, and proprioception. These processes hinge on somatotopic, spatial, and temporal patterning in the peripheral nervous system (PNS) and central nervous system (CNS) during neurogenesis, synaptogenesis, and postnatal circuit refinement. Perturbation of somatosensory development has been shown to disrupt normal tactile processing, resulting in touch avoidance, anxiety, cognitive dysfunction, and aberrant social behaviors seen in patients diagnosed with neurodevelopmental conditions such as autism spectrum disorder (ASD; Tasnim et al., 2024). However, mechanisms underlying homeostatic spinal cord development are not well known.⇓ Figure 1. Microglial phagocytosis of A-fiber synapses in the dorsal horn during early postnatal development (P1–3) influences mature dorsal horn synaptic density and sensitivity to touch. A , Typical spinal cord dorsal horn development leads to a reduction in cutaneous receptive field size and sensitivity to touch. B , Tmem16f conditional knock-out (cKO) pups exhibit reduced microglial phagocytosis of A-fiber terminals in laminae I-II (left). Adults retain extraneous VGLUT1+ synapses, large hindpaw receptive fields specific to dynamic touch, and hyporesponsive wide dynamic range (WDR) neurons encoding both static and dynamic touch (right). Created in BioRender (Eschenbacher 2024). Immature neuronal circuits have numerous superfluous synaptic connections between predominantly excitatory neurons that have spontaneous and low-threshold firing properties. Consequently, these circuits exhibit hyperexcitability, which is refined during postnatal development by targeted restructuring to form a mature circuit that is both sensitive and tolerant enough to perceive and react to stimuli with a range of properties and intensities (Fig. 1 A; Abraira and Ginty, 2013; Koch and Fitzgerald, 2013). Although research into the mechanisms underlying such refinement in the brain has shown that activity-dependent postnatal synapse modification is carried out by microglia (Durán Laforet and Schafer, … Correspondence should be addressed to Kayla M. Eschenbacher at kaylae{at}genetics.utah.edu.