During postnatal development, visual experience initiates synaptic plasticity mechanisms that guide the refinement and maturation of visual cortex necessary to support the emergence of visual functions. Lack of normal visual experience during development can lead to vision loss, a condition called amblyopia. Additionally, even if our vision developed properly early in life, our vision naturally declines as we age. The mechanisms underlying vision loss associated with amblyopia and aging are not fully understood, and the studies in this thesis were designed to increase our understanding of the neural basis of vision loss through the linkage of synaptic protein expression to changes in vision. In the first part of this thesis, I examined the impact of monocular deprivation on synaptic proteins in visual cortex, and on vision. Using Western blot analysis I showed that monocular deprivation causes a rapid, and sustained loss of AMPAR proteins in the region of cat visual cortex representing the center of vision. Because AMPARs play a key role mediating visual processing, I extended these findings by using behavioural measurements to show that the sustained loss of AMPARs in the central region is correlated with long-lasting binocular acuity deficits that are most severe in the center of vision. These findings showed that disrupting binocular vision early in development leads to experience-dependent changes that are greatest in the center of vision. In the second part of this thesis, I examined age-related changes in the expression of a group of synaptic proteins associated with glutamatergic and GABAergic synapses. I found an age-related decline in the expression of Ube3A, a protein necessary for ocular dominance plasticity, across sensory and non-sensory regions of cat, macaque, and human cortex. However, there was a selective loss of Ube3A relative to other synaptic proteins that occurred only in human cortex. Finally, I found a substantial age-related decline in expression of both glutamatergic and GABAergic synaptic proteins across cat visual cortex, suggesting fewer synapses in aging. Together, the findings from this thesis provide new insight into the neural basis of vision loss, and provide a foundation for the development of therapeutic interventions for cortical vision loss. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/16408 |
| Date | 11 1900 |
| Creators | Williams, Ceinwen Kate |
| Contributors | Murphy, Kathryn, Neuroscience |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
Page generated in 0.0022 seconds