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

Sachiko Murase,Dan Winkowski,Patrick O Kanold,Ji Liu,Elizabeth M Quinlan

doi:10.7554/elife.52503

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.

Highlights

An imbalance in the quality of visual inputs between the two eyes during development induces amblyopia, a developmental disorder affecting up to 4% of the world’s population (Levi et al, 2015)
Ex vivo imaging revealed punctate MMP2/9 activity in the deprived and non-deprived V1b (Fig. 1A) that was similar in size, density and fluorescence intensity as we previously described in binocular adult mice (Murase et al, 2017)
To test the hypothesis that LRx to the amblyopic cortex induces extracellular matrix (ECM) degradation, we examined the distribution of Wisteria floribunda agglutinin (WFA), a plant lectin that binds to the CS side chains of chondroitin sulfate proteoglycans (CSPGs), combined with immunoreactivity for Agg and PV

Summary

Introduction

An imbalance in the quality of visual inputs between the two eyes during development induces amblyopia, a developmental disorder affecting up to 4% of the world’s population (Levi et al, 2015). In animal models, prolonged monocular deprivation induces severe amblyopia, characterized by a significant decrease in the strength and selectivity of neuronal responses in the deprived visual cortex (Harwerth et al, 1983). (Montey et al, 2013)(Fong et al, 2016) and a significant loss of spatial acuity through the deprived eye (Wiesel and Hubel, 1963) (Harwerth et al, 1983)(Liao et al., 2011)(Montey et al, 2013). Chronic monocular deprivation (cMD) significantly decreases the density of dendritic spines on pyramidal neurons in deprived V1b (Montey and Quinlan, 2011) and results in a 60% decrease in the thalamic component of the visually evoked potential (VEP, ( Montey and Quinlan, 2011)).

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Results

Conclusion