THE REGULATION OF EXCITATORY SYNAPSES ONTO PARVALBUMIN-POSITIVE INTERNEURONS BY BRIEF MONOCULAR DEPRIVATION IN THE JUVENILE VISUAL CORTEX

Abstract

Amblyopia, a visual system disorder that affects about two percent of the world's population, is characterized by the asymmetric reception of visual input across the two eyes. It leads to visual deficits in acuity detection and depth perception in the amblyopic eye and causes a shift in preference of visual input towards the uncompromised eye. The mechanisms that underlie synaptic deficits in amblyopia are partially understood. Therefore, identifying factors contributing to amblyopia during the developmental critical period remains a priority. Amblyopia therapies become less effective once humans reach eight years old due to the maturation of parvalbumin-positive interneurons (PV+ INs) in the visual circuit. However, altering excitatory inputs onto PV+ INs can induce layer-specific synaptic plasticity following monocular deprivation (MD), a treatment that mimics amblyopia. Cleavage of the structural barriers around PV+ INs can also reactivate plasticity, suggesting that enzymatic activity within the visual cortex could be used in amblyopia therapy. Here, I investigate the role of tumor necrosis factor alpha converting enzyme (TACE) in the juvenile visual cortex following MD. I hypothesize that reduced excitatory synaptic contacts onto PV+ INs in the deprived hemisphere is governed by upregulated TACE activity. FRET-based fluorescence was utilized to determine the spatial distribution and localization of TACE activity within the juvenile cortex. First, I demonstrate that TACE activation decreases in the compromised hemisphere following MD, independent of presynaptic excitatory biomarkers. Second, I show that TACE activity within Layer 2/3 of the visual cortex was time-dependent and unilaterally disrupted by MD. Lastly, I investigated the prevalence of TACE substrate neuronal pentraxin receptor (NPR) and found that NPR fluorescence increased in the deprived hemisphere following MD, independent of changes in excitatory synaptic contacts. Although the involvement of TACE within the excitatory disconnection pathway was disproven, the in vivo application of FRET-based biomarkers provides new insight into enzyme-specific therapeutics for amblyopia and other visual system disorders.