![]() ![]() However, recovery from MD is incomplete in cats that receive ChABC following eye opening ( Vorobyov et al., 2013). Treatment of adult V1 with the bacterial enzyme chondroitinase ABC (ChABC), which cleaves the CS side chains from the CSPGs, reactivates robust plasticity in rats ( Pizzorusso et al., 2006 Pizzorusso et al., 2002). Manipulations that reduce the integrity of the ECM/PNNs have been repeatedly shown to enhance plasticity in V1 and elsewhere. PNNs also accumulate molecules that regulate PV + IN excitability and maturation ( Beurdeley et al., 2012 Chang et al., 2010 Hou et al., 2017). Importantly, ECM molecules condense into perineuronal nets (PNNs) around a subset of PV + INs, limiting their structural and functional plasticity by imposing a physical constraint and providing binding sites for molecules that inhibit neurite outgrowth ( Dickendesher et al., 2012 Frantz et al., 2016 Stephany et al., 2016 Vo et al., 2013). ![]() Developmental changes in synaptic plasticity are also associated with the composition and density of the ECM, comprised of chondroitin sulfate proteoglycans (CSPGs) and hyaluronic acid, linked via cartilage link protein and tenascins ( Carulli et al., 2010 Celio and Chiquet-Ehrismann, 1993 Morawski et al., 2014). PV + INs mediate the perisomatic inhibition of pyramidal neurons, thereby exerting powerful control of neuronal excitability and spike-timing dependent synaptic plasticity. Strong evidence demonstrates that developmental changes in the induction of synaptic plasticity in V1 are regulated by the maturation of fast-spiking basket interneurons (INs) that express the Ca 2+ binding protein parvalbumin (PV) ( Gu et al., 2016 Gu et al., 2013 Morishita et al., 2015 Stephany et al., 2016 Sun et al., 2016). The loss of synaptic plasticity in the primary visual cortex with age is thought to significantly impede the reversal of amblyopic deficits ( Tailor et al., 2017). cMD also significantly decreases the density of dendritic spines on pyramidal neurons in deprived binocular primary visual cortex (V1b) ( Montey and Quinlan, 2011) and induces a 60% decrease in the thalamic component of the visually evoked potential (VEP, ). Additionally, following prolonged monocular deprivation, neurons in the dorsal lateral geniculate nucleus (dLGN) that project to deprived binocular visual cortex have lower metabolism ( Kennedy et al., 1981) and smaller somata ( Duffy et al., 2018). In rats, spatial acuity in the deprived eye is undetectable following chronic monocular deprivation (cMD) initiated at eye opening ( Eaton et al., 2016). 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 ( Fong et al., 2016 Harwerth et al., 1983 Montey et al., 2013) and a significant loss of spatial acuity through the deprived eye ( Harwerth et al., 1983 Liao et al., 2011 Montey et al., 2013). ![]() IntroductionĪn 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). The homeostatic reduction of the MMP2/9 activation threshold by DE enables visual input from the amblyopic pathway to trigger robust perisynaptic proteolysis. 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. 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. ![]() 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. However, it was unknown if a visual system compromised by amblyopia could engage this pathway. Previously we showed that perisynaptic proteolysis by MMP9 mediates the enhancement of plasticity by LRx in binocular adult mice (Murase et al., 2017). 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. ![]()
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