Brainstem local microglia induce whisker map plasticity in the thalamus after peripheral nerve injury.

Whisker deafferentation in mice 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.