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|Title:||Characterization and Comparison of Neuroplasticity Mechanisms in Rat and Human Cortex|
|Abstract:||<p>Neuroplasticity describes the capacity and mechanisms underlying experience driven changes in function and organization of neural connections. Animal models have uncovered many mechanisms that control neuroplasticity, such as the E-I balance and structural brakes, and have identified the timing of critical periods in development when the degree of plasticity is high. Ocular dominance plasticity in visual cortex is the preeminent model for studying plasticity. Its a useful paradigm because it links from molecular mechanisms to anatomical and physiological changes, to visual perception and the human visual disorder of lazy-eye (amblyopia). Treatments for amblyopia have traditionally had poor efficacy (~50%), but recently, a number of interventions have shown they are able to re-instate ocular dominance plasticity in older rats. Little is known, however, about developmental translation of the mechanisms that control the critical period plasticity between rat and human. To address this, I conducted a series of experiments in human and rat cortices to characterize and compare development of a set of proteins involved in regulating neuroplasticity. First, I used Western blot analysis to quantify the development of Synapsin, Synaptophysin, PSD-95, and Gephyrin in rat and human cortex, compared the development of these proteins between species and determined the translation from rat to human cortical development. These studies revealed that total protein expression is comparable in rat and human visual cortex during early development, and that synaptic age is similar between species at comparable stages of visual system development. Second, I quantified development of GABAergic mechanisms in human visual cortex across the lifespan. I found complex and prolonged changes in these mechanisms that help to highlight stages of human cortical development. Third, I quantified the effects of reinstating ocular</p> <p>dominance plasticity in adult rats using fluoxetine on the mechanisms known to facilitate the onset and closure of the critical period. This study showed that fluoxetine reduces the brakes on plasticity, and re-set the E-I balance. The results from my Ph.D. thesis experiments provide detailed characterization of synaptic development in human visual cortex, and a new comparison for studying humans and rat cortical development. Together my studies have found new insights about the capacity for neuroplasticity in human visual cortex, a new way to translate cortical developmental stages between species, and that re-instating plasticity in adult cortex effects both the brakes and plasticity promoting mechanisms.</p>|
|Appears in Collections:||Open Access Dissertations and Theses|
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