PT  - JOURNAL ARTICLE
AU  - Justin L. Balsor
AU  - David G. Jones
AU  - Kathryn M. Murphy
TI  - Classification of visual cortex plasticity phenotypes following treatment for amblyopia
AID  - 10.1101/554576
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 554576
4099  - http://biorxiv.org/content/early/2019/02/19/554576.short
4100  - http://biorxiv.org/content/early/2019/02/19/554576.full
AB  - 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.