Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex

Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse V1, which allows recovery from amblyopia. Previously we showed that LRx-induced perisynaptic proteolysis of extracellular matrix (ECM) by MMP9 mediates the enhanced plasticity in binocular adult mice (Murase et al., 2017). However, it is unknown if a visual system compromised by amblyopia could engage this pathway. Here we show that LRx to adult amblyopic mice induces perisynaptic MMP2/9 activity and ECM degradation in the deprived and non-deprived V1. LRx restricted to the amblyopic eye induces equally robust MMP2/9 activity at thalamo-cortical synapses and ECM degradation in deprived V1. Two-photon live imaging demonstrates that the history of visual experience regulates MMP2/9 activity in V1, and that DE lowers the threshold for the proteinase activation. The homeostatic reduction of MMP2/9 activation threshold by DE enables the visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.