Microglia enable cross-modal plasticity by removing inhibitory synapses

Cross-modal plasticity is the repurposing of brain regions associated with deprived sensory inputs to improve the capacity of other sensory modalities. The functional mechanisms of cross-modal plasticity can indicate how the brain recovers from various forms of injury and how different sensory modalities are integrated. Here, we demonstrate that rewiring of the microglia-mediated local circuit synapse is crucial for cross-modal plasticity induced by visual deprivation (monocular deprivation [MD]). MD relieves the usual inhibition of functional connectivity between the somatosensory cortex and secondary lateral visual cortex (V2L). This results in enhanced excitatory responses in V2L neurons during whisker stimulation and a greater capacity for vibrissae sensory discrimination. The enhanced cross-modal response is mediated by selective removal of inhibitory synapse terminals on pyramidal neurons by the microglia in the V2L via matrix metalloproteinase 9 signaling. Our results provide insights into how cortical circuits integrate different inputs to functionally compensate for neuronal damage. [Display omitted] •Monocular deprivation in mice results in enhanced somatosensory discrimination•Visual deprivation increases visual cortex (V2L) excitability during whisker stimulation•Microglia phagocytose local inhibitory synapses to unmask cross-modal plasticity•Matrix metalloproteinase 9 activity in V2L is required for cross-modal plasticity Hashimoto et al. demonstrate that microglia are required for cross-modal plasticity after monocular deprivation. Through metalloprotease-dependent phagocytosis of inhibitory inputs, microglia enhance visual cortex excitability during whisker stimulation to enhance somatosensory discrimination ability. These results provide mechanisms for neural plasticity that can mediate behavioral adaptations following sensory loss.