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Homeostatic regulation of perisynaptic matrix metalloproteinase 9 (MMP9) activity in the amblyopic visual cortex
Sachiko Murase1,2, Dan Winkowski1,2, Ji Liu1,2
1Department of Biology, University of Maryland, College Park, United States.
Abstract:
Dark exposure (DE) followed by light reintroduction (LRx) reactivates robust synaptic plasticity in adult mouse primary visual cortex (V1), which allows subsequent recovery from amblyopia. Previously we showed that perisynaptic proteolysis by MMP9 mediates the enhancement of plasticity by LRx in binocular adult mice (Murase et al., 2017). However, it was 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 extracellular matrix (ECM) degradation in deprived and non-deprived V1. Indeed, LRx restricted to the amblyopic eye is sufficient to induce 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 the MMP2/9 activation threshold by DE enables visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis.
Insights
Light reintroduction reactivates synaptic plasticity in amblyopic mice by activating MMP2/9 proteolysis. Dark exposure lowers the activation threshold, enabling recovery from amblyopia.
Area of Science:
- Neuroscience
- Molecular Biology
- Visual System Research
Background:
- Dark exposure (DE) followed by light reintroduction (LRx) enhances synaptic plasticity in the adult mouse primary visual cortex (V1).
- Matrix metalloproteinase 9 (MMP9) mediates plasticity enhancement by LRx in binocular mice.
- The role of this pathway in amblyopic visual systems was previously unknown.
Purpose of the Study:
- To investigate if the visual system of amblyopic adult mice can engage the MMP9 pathway.
- To determine the role of MMP2/9 activity and extracellular matrix (ECM) degradation in amblyopic V1 following LRx.
- To explore how visual experience history and DE affect MMP2/9 activity.
Main Methods:
- Administering LRx to adult amblyopic mice.
- Assessing perisynaptic MMP2/9 activity and ECM degradation in V1.
- Using two-photon live imaging to observe MMP2/9 activity dynamics.
- Restricting LRx to the amblyopic eye to assess pathway specificity.
Main Results:
- LRx in adult amblyopic mice induced perisynaptic MMP2/9 activity and ECM degradation in both deprived and non-deprived V1.
- LRx to the amblyopic eye alone triggered significant MMP2/9 activity and ECM degradation in deprived V1.
- Visual experience history regulates MMP2/9 activity, with DE lowering the activation threshold.
- DE facilitates MMP2/9 activation by visual input from the amblyopic pathway.
Conclusions:
- The MMP2/9 pathway is engaged in adult amblyopic mice following LRx, contributing to synaptic plasticity.
- DE plays a crucial homeostatic role by reducing the MMP2/9 activation threshold, enabling recovery from amblyopia.
- Targeting MMP2/9 activity presents a potential therapeutic strategy for amblyopia treatment.
