Microglia enable cross-modal plasticity by removing inhibitory synapses
Akari Hashimoto, Nanami Kawamura, Etsuko Tarusawa, Ikuko Takeda, Yuki Aoyama, Nobuhiko Ohno, M. Inoue, Mai Kagamiuchi, Daisuke Kato, Mami Matsumoto, Yoshihiro Hasegawa, Junichi Nabekura, Anne Schaefer, Andrew J. Moorhouse, Takeshi Yagi, Hiroaki Wake
Abstract
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.