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Local neuron-microglia interaction in the brainstem induces whisker map plasticity in the thalamus after peripheral nerve injury.
Yoshifumi Ueta (Yoshifumi Ueta, Mariko Miyata)

Peripheral nerve injury develops referred pain, which might attribute to maladaptive plasticity in the central nervous system. In mice, whisker deafferentation by cutting peripheral whisker sensory nerve disrupts topographic connectivity from the brainstem to the thalamic ventral posteromedial nucleus (VPM), which represents whisker map, by recruiting ‘ectopic’ axons carrying non-whisker information in VPM. However, mechanisms inducing this plasticity remain largely unknown. Here, we show the role of region-specific microglia in the brainstem principal trigeminal nucleus (Pr5), a whisker sensory-recipient region, in VPM whisker map plasticity. Systemic or local manipulation of microglial activity reveals that microglia in Pr5, but not in VPM, are necessary and sufficient for recruiting ectopic axons in VPM. Deafferentation causes membrane hyperexcitability of Pr5 neurons dependent on microglia. Inactivation of Pr5 neurons abolishes this somatotopic reorganization in VPM. Additionally, microglial depletion prevents deafferentation-induced ectopic mechanical hypersensitivity. Our results indicate that local microglia in the brainstem induce peripheral nerve injury-induced plasticity of map organization in the thalamus, and suggest that microglia are potential therapeutic targets for peripheral nerve injury-induced mechanical hypersensitivity like referred pain.

Ueta Y, Miyata M. Brainstem local microglia induce whisker map plasticity in the thalamus after peripheral nerve injury. Cell Reports 34(10): 108823, 2021.

<Figure Legends>
Whisker sensory nerve injury induces microglial accumulation in the whisker region of the brainstem. Microglial accumulation contributes to membrane hyperexcitability of brainstem neurons. This neuron-microglia interaction is necessary for recruitment of ectopic non-whisker-originated axons in the whisker region of the thalamus. Whisker map reorganization in the thalamus closely associates with ectopic mechanical hypersensitivity to lower jaw tactile stimulation in mice. Microglial depletion can prevent all of changes in membrane excitability of brainstem neurons, whisker map reorganization in the thalamus, and ectopic mechanical hypersensitivity.

Division of Neurophysiology, Department of Physiology, School of Medicine, Tokyo Women’s Medical University, Japan