Abstract
A fundamental regulator of neuronal network development and plasticity is the extracellular matrix (ECM) of the brain. The ECM provides a scaffold stabilizing synaptic circuits, while the proteolytic cleavage of its components and cell surface proteins are thought to have permissive roles in the regulation of plasticity. The enzymatic proteolysis is thought to be crucial for homeostasis between stability and reorganizational plasticity and facilitated largely by a family of proteinases named matrix metalloproteinases (MMPs). Here, we investigated whether MMP2 and MMP9 play a role in mediating adult primary visual cortex (V1) plasticity as well as stroke-induced impairments of visual cortex plasticity in mice. In healthy adult mice, selective inhibition of MMP2/9 for 7 d suppressed ocular dominance plasticity. In contrast, brief inhibition of MMP2/9 after a cortical stroke rescued compromised plasticity. Our data indicate that the proteolytic activity of MMP2 and MMP9 is critical and required to be within a narrow range to allow adult visual plasticity.SIGNIFICANCE STATEMENT Learning and recovery from injuries depend on the plasticity of neuronal connections. The brain's extracellular matrix (ECM) provides a scaffold for stabilizing synaptic circuits, while its enzymatic proteolysis is hypothesized to regulate homeostasis between stability and reorganizational plasticity. ECM digestion is facilitated by a family of matrix metalloproteinases (MMPs). Here, we show that treatments that inhibit MMP2/9 can either inhibit or rescue cortical plasticity depending on cortical state: in the visual cortex of healthy adult mice, inhibition of MMP2/9 suppressed cortical plasticity. In contrast, brief inhibition of MMP2/9 after a stroke rescued compromised plasticity. Our data provide strong evidence that an optimal level of MMP2/9 proteolytic activity is crucial for adult visual plasticity.