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)

Visual information about the form of an object and its movement in the world can be processed independently. These processing streams must be combined, since our visual experience is of a unitary stream of information. Studies of interactions between motion and form processing can therefore provide insight into how this combination occurs. The present thesis explored two such interactions between motion and spatial coding in human vision. The title of the thesis, “Pencils and Erasers”, serves as an analogy for the thesis’ principal findings. I investigate one situation in which moving patterns can impair the visibility of stationary forms, and another in which the visibility of form is enhanced by motion. In motion-induced blindness (MIB; Bonneh, Cooperman, & Sagi, 2001), salient stationary objects can seem to disappear intermittently from awareness when surrounded by moving features. Static forms proximate to motion can be “erased” from awareness. The thesis contributes to the answer to a simple question: why does MIB happen? My interpretation of this phenomenon emphasises the possible functional benefit of such an eraser around moving form: to suppress artifacts of visual processing from awareness. Chapter 2 demonstrates that motion per se is not required for MIB (Wallis & Arnold, 2008). MIB depends on the rate of luminance change over time, rather than the velocity (or change in position) of the inducing mask. MIB can therefore be characterised as a temporal inhibition, which does not critically depend on direction selective (motion) mechanisms. A similar mechanism of temporal inhibition that does not depend on motion is that which suppresses motion streaks from awareness. The human visual system integrates information over time. Consequently, moving image features produce smeared signals, or “motion streaks”, much like photographing a moving object using a slow shutter speed. We do not experience motion streaks as much as might be expected as they are suppressed from awareness in most circumstances. Evidence suggests that this suppression is enacted by a process of local temporal inhibition, and does not depend on motion mechanisms – much like MIB. These similarities led us to propose that MIB and motion streak suppression might reflect the same mechanism. In the case of MIB, physically present static targets may not be differentiated from signals arising from within the visual system, such as a motion streak. Chapter 3 of the thesis presents four converging lines of evidence in support of this hypothesis (Wallis & Arnold, 2009). The link between MIB and a mechanism of temporal inhibition that serves to suppress motion streaks is further strengthened by a recent report from our laboratory of a new visual illusion, Spatio-Temporal Rivalry (STR; Arnold, Erskine, Roseboom, & Wallis, in press), that is included in the present thesis as an appendix. Why does MIB occur? I suggest that at its base level, MIB reflects the activity of this simple visual mechanism of temporal inhibition (see Gorea & Caetta, 2009). This mechanism might usually serve a functional role in everyday vision: for example, by suppressing the perception of motion streaks. The second motion and form interaction investigated in the thesis represents a situation in which motion can improve form sensitivity. In some situations, observing a moving pattern can objectively improve sensitivity to that pattern after the offset of motion. The visual system can “pencil in”, or improve the visibility of, subsequent visual input. When a form defined by its motion relative to the background ceases to move, it does not seem to instantly disappear. Instead, the form is perceived to remain segregated from the background for a short period, before slowly fading. It is possible that this percept represents a consequence of bias or expectation, not a modulation of static form visibility by motion. Contrary to this possibility, Wallis, Williams and Arnold (2009) demonstrate that alignment sensitivity to spatial forms is improved by pre-exposure to moving forms (Chapter 4). I suggest that the subjective persistence of forms after motion offset and this spatial facilitation may represent two consequences of the same signal. The experiments herein address one situation in which moving patterns can impair the visibility of stationary forms and one in which moving patterns enhance the visibility of stationary forms. Therefore, the present thesis characterises two interactions between form and motion processing in human vision. These mechanisms of “pencil” and “eraser” facilitate the clear perception of objects in our visual world.

Alterações macro e microvasculares ocorrem no Diabetes Mellitus (DM). A Retinopatia Diabética (RD) é uma complicação bem prevalente do DM e resulta de microangiopatia generalizada no tecido retiniano que, em diferentes estágios da doença, se observa como edema local, exsudatos, formação de neovasos e hemorragias, sendo a principal causa de cegueira na faixa etária de 20 a 74 anos. Alguns fatores angiogênicos são apontados como possíveis mediadores no desenvolvimento das alterações microvasculares no DM. Dentre eles, a Eritropoietina (EPO), hormônio glicoproteico, possui expressão mediada por alelos específicos do gene EPO. Determinados perfis genéticos para três SNPs-single nucleotide polymorphisms do gene EPO (rs1617640, rs507392, rs551238) encontram-se associados com maiores concentrações de EPO no humor vítreo de pacientes diabéticos com RD, o que pode ser indicativo da relação entre determinado genótipo de risco (TTA) e o desenvolvimento de tal comorbidade. O presente trabalho pretendeu investigar a associação entre o genótipo considerado de risco para o desenvolvimento de RD e alterações funcionais na visão de cores de pessoas com diagnóstico de DM. Tal estudo contou com uma amostra de 95 diabéticos (49 mulheres e 46 homens, média de idade: 48,33 anos; DP: 16,90), com um total de 31 DM tipo 1 e 64 tipo 2 e 114 controles (73 mulheres e 41 homens, média de idade: 38,38 anos; DP: 12,81). Foi realizada avaliação através de teste psicofísico (Cambridge Colour Test CCT), que visou medir o limiar de discriminação nos três eixos de confusão de cores e sequenciamento genético, a partir de amostras de sangue. Para os diabéticos, no eixo de confusão protan, os resultados mostraram uma piora de desempenho para o genótipo TTA/GCC (p= 0,048), com relação aos controles. No eixo de confusão deutan, não houve diferença para qualquer dos genótipos (p= 0,0207), enquanto que para o eixo tritan, o genótipo TTA/GCC esteve associado a uma piora de desempenho (p=0,014). Para os controles, não houve diferença entre os genótipos. Assim, os resultados mostraram uma piora na visão de cores de pacientes DM, associada ao haplótipo TTA/GCC / Diabetic Retinopathy (DR), a prevalent complication of diabetes, is the leading cause of blindness among those aged 20-74 years. Micro and macrovascular changes occur in Diabetes Mellitus (DM) with DR being the most common among these vascular complications, resulting in generalized retinal microgangiopathy. At different stages of the disease, localized edema, exudates and hemorrhages occur. Several pro-angiogenic factors have been suggested as possible mediators in the development of these microvascular changes. Among them is erythropoietin (EPO), a glycoprotein hormone whose expression is mediated by specific alleles of the EPO gene. Specific genetic profiles for three single nucleotide polymorphisms (SNPs) in the EPO gene (rs1617640, rs507392, rs551238) are associated with larger EPO concentrations in the vitreous humor of diabetic patients with RD. This association indicates a possible relationship between the identified genotypes (TTA) and the comorbidity´s development. This work aimed to investigate the association between genotypes considered at risk for the development of DR and functional changes in color vision among individuals diagnosed with DM. Thus, this study included a sample of 95 diabetic patients (49 women and 46 men, average age: 48.33 years; SD: 16.90), with a total of 31 DM type 1 and 64 type 2 and 114 controls (73 women and 41 men, average age: 38.38 years; SD: 12.81). Evaluation was performed using a psychophysical test (Cambridge Colour Test -CCT), to measure the discrimination threshold in three-color confusion axes in addition to genetic sequencing. In the protan axis of confusion color, performance among diabetics with the TTA/GCC genotype was significantly lower (p=0.048) than those in the control group. The results showed a poorer performance among those with the TTA / GCC genotype (p = 0.048), compared to controls. In deutan axis confusion, there was no difference among any of the genotypes (p = 0.0207), while for the tritan axis, the TTA / GCC genotype was associated with a poorer performance (p = 0.014). For the controls, there was no difference between genotypes. Thus, the results showed a worsening in color vision among DM patients associated with TTA / GCC haplotype

Alterações macro e microvasculares ocorrem no Diabetes Mellitus (DM). A Retinopatia Diabética (RD) é uma complicação bem prevalente do DM e resulta de microangiopatia generalizada no tecido retiniano que, em diferentes estágios da doença, se observa como edema local, exsudatos, formação de neovasos e hemorragias, sendo a principal causa de cegueira na faixa etária de 20 a 74 anos. Alguns fatores angiogênicos são apontados como possíveis mediadores no desenvolvimento das alterações microvasculares no DM. Dentre eles, a Eritropoietina (EPO), hormônio glicoproteico, possui expressão mediada por alelos específicos do gene EPO. Determinados perfis genéticos para três SNPs-single nucleotide polymorphisms do gene EPO (rs1617640, rs507392, rs551238) encontram-se associados com maiores concentrações de EPO no humor vítreo de pacientes diabéticos com RD, o que pode ser indicativo da relação entre determinado genótipo de risco (TTA) e o desenvolvimento de tal comorbidade. O presente trabalho pretendeu investigar a associação entre o genótipo considerado de risco para o desenvolvimento de RD e alterações funcionais na visão de cores de pessoas com diagnóstico de DM. Tal estudo contou com uma amostra de 95 diabéticos (49 mulheres e 46 homens, média de idade: 48,33 anos; DP: 16,90), com um total de 31 DM tipo 1 e 64 tipo 2 e 114 controles (73 mulheres e 41 homens, média de idade: 38,38 anos; DP: 12,81). Foi realizada avaliação através de teste psicofísico (Cambridge Colour Test CCT), que visou medir o limiar de discriminação nos três eixos de confusão de cores e sequenciamento genético, a partir de amostras de sangue. Para os diabéticos, no eixo de confusão protan, os resultados mostraram uma piora de desempenho para o genótipo TTA/GCC (p= 0,048), com relação aos controles. No eixo de confusão deutan, não houve diferença para qualquer dos genótipos (p= 0,0207), enquanto que para o eixo tritan, o genótipo TTA/GCC esteve associado a uma piora de desempenho (p=0,014). Para os controles, não houve diferença entre os genótipos. Assim, os resultados mostraram uma piora na visão de cores de pacientes DM, associada ao haplótipo TTA/GCC / Diabetic Retinopathy (DR), a prevalent complication of diabetes, is the leading cause of blindness among those aged 20-74 years. Micro and macrovascular changes occur in Diabetes Mellitus (DM) with DR being the most common among these vascular complications, resulting in generalized retinal microgangiopathy. At different stages of the disease, localized edema, exudates and hemorrhages occur. Several pro-angiogenic factors have been suggested as possible mediators in the development of these microvascular changes. Among them is erythropoietin (EPO), a glycoprotein hormone whose expression is mediated by specific alleles of the EPO gene. Specific genetic profiles for three single nucleotide polymorphisms (SNPs) in the EPO gene (rs1617640, rs507392, rs551238) are associated with larger EPO concentrations in the vitreous humor of diabetic patients with RD. This association indicates a possible relationship between the identified genotypes (TTA) and the comorbidity´s development. This work aimed to investigate the association between genotypes considered at risk for the development of DR and functional changes in color vision among individuals diagnosed with DM. Thus, this study included a sample of 95 diabetic patients (49 women and 46 men, average age: 48.33 years; SD: 16.90), with a total of 31 DM type 1 and 64 type 2 and 114 controls (73 women and 41 men, average age: 38.38 years; SD: 12.81). Evaluation was performed using a psychophysical test (Cambridge Colour Test -CCT), to measure the discrimination threshold in three-color confusion axes in addition to genetic sequencing. In the protan axis of confusion color, performance among diabetics with the TTA/GCC genotype was significantly lower (p=0.048) than those in the control group. The results showed a poorer performance among those with the TTA / GCC genotype (p = 0.048), compared to controls. In deutan axis confusion, there was no difference among any of the genotypes (p = 0.0207), while for the tritan axis, the TTA / GCC genotype was associated with a poorer performance (p = 0.014). For the controls, there was no difference between genotypes. Thus, the results showed a worsening in color vision among DM patients associated with TTA / GCC haplotype