Abstract
Monocular deprivation (MD) during the critical period (CP) has enduring effects on visual acuity and the functioning of the visual cortex (V1). This experience-dependent plasticity has become a model for studying the mechanisms, especially glutamatergic and GABAergic receptors, that regulate amblyopia. Less is known, however, about treatment-induced changes to those receptors and if those changes differentiate among treatments that support good recovery of acuity versus persistent acuity deficits. Here we studied the effects of 3 treatments for MD started during the CP (n=24, 10 male and 14 female). Two treatments (reverse occlusion -- RO, binocular deprivation -- BD) resulted in poor acuity, but one treatment (binocular vision --BV) promoted good acuity. We classified plasticity phenotypes using the expression of a collection of glutamatergic and GABAergic receptor subunits in V1. Analyzing individual proteins showed an intricate pattern of changes, but principal component analysis identified features that we used to construct the plasticity phenotypes and classify treatments into clusters suggesting adaptive versus maladaptive plasticity. The RO plasticity phenotype was similar to an adult pattern with high expression of GluA2, while the BD phenotypes were dominated by GABAAα1, highlighting that multiple plasticity phenotypes can underlie persistent acuity deficits. In contrast, BV for 2-4 days promoted recovery of a phenotype resembling CP plasticity, but only one feature, the GluN2A:GluA2 balance, returned to normal levels. This suggests that balancing homeostatic and Hebbian mechanisms is needed for good visual recovery. These findings and the plasticity phenotyping approach may be useful for classifying different forms of persistent amblyopia and identifying new treatment targets.
Footnotes
Kathryn Murphy, Department of Psychology, Neuroscience & Behavior, McMaster University, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada
Funding Sources: NSERC Grant RGPIN-2015-06215 awarded to KM, Woodburn Heron OGS awarded to JB.
Data Availability: The data used to support the findings of this study are available from the corresponding author upon request.