Graduation Year

2021

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Medicine

Major Professor

Christopher Passaglia, Ph.D.

Co-Major Professor

Jay Dean, Ph.D.

Committee Member

Radouil Tzekov, M.D., Ph.D.

Committee Member

Thomas Taylor-Clark, Ph.D.

Committee Member

Kevin Nash, Ph.D.

Keywords

Psychophysics, optomotry, receptive field, animal model

Abstract

Retinal Ganglion Cells (RGCs) are the sole cells through which visual information is transmitted from the eye to the brain. As such, RGC dysfunction has a dramatic effect on vision and perception. Retinal neurodegenerative diseases, such as glaucoma, are one of the leading causes of blindness worldwide. The study of these diseases requires well-characterized models in order to swiftly and effectively develop diagnostic tools and therapeutics. This dissertation aims to characterize specific properties of the visual system of the Brown-Norway rat. First, visual processing was evaluated in awake, freely moving rats. Contrast sensitivities of Brown-Norway rats were characterized by discrimination-driven behavior and by the optomotor reflex. Contrast sensitivities were examined at a range of spatial and temporal frequencies. The peak contrast, spatial, and temporal sensitivities characterized by the optomotor reflex were markedly lower than those characterized by the discrimination-driven task but match neurons of the superior colliculus. Second, the temporal filtering of the receptive field (RF) center and surround of RGC cell types was characterized by in vivo extracellular recording. RGCs were found to exhibit nonlinear properties similar to cell types found in other species, and different RGC cell types exhibited different temporal filtering properties. Receptive field center properties were compared to surround properties and surround stimulation caused RGCs to fire at higher temporal frequencies than center-optimized stimulation. Lastly, the flash, flicker, and pattern electroretinograms (ERG) were compared to the activity of RGCs in order to identify non-invasive measures to quantify RGC health and activity. RGCs were found to fire synchronously with oscillatory potentials of the flash ERG- a phenomenon that has not been described before. Previous studies have demonstrated that the temporal frequency response of the flicker ERG can distinguish between the On- and Off- retinal pathways in primates and in mice, but this distinction was found to not extend to the rat. Alternatively, a reversing pattern stimulus generated frequency-dependent differences in On- and Off-type RGCs.

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