Date on Master's Thesis/Doctoral Dissertation
8-2024
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Anatomical Sciences and Neurobiology
Degree Program
Anatomical Sciences and Neurobiology, PhD
Committee Chair
Guido, William
Committee Member
McGee, Aaron
Committee Member
Cai, Jun
Committee Member
Bickford, Martha
Committee Member
McCall, Maureen
Author's Keywords
CVI; hypoxia; injury; brain; development
Abstract
Cerebral/cortical visual impairment (CVI) is a disorder most often caused by perinatal hypoxic injury to the developing brain. CVI is the leading cause of childhood visual impairment in developed nations, encompassing deficits in many aspects of vision including visual acuity, contrast sensitivity, and object recognition. The pathophysiology of CVI is not well understood because no animal model currently exists to study this disorder. Because there is no animal model, the pathophysiology of CVI is poorly understood. Here, we developed a murine early postnatal hypoxic model of CVI by exposing mice to 9.5% O2 at postnatal day (P)3 for a duration of 7, 14, or 30 days. As adults (>P40), we tested the motor function, visual acuity, and binocular depth perception of normoxic control mice as well as 7, 14, and 30 day hypoxic mice. Then, we examined the pattern of eye specific segregation of retinogeniculate afferents in the dorsal lateral geniculate nucleus of the thalamus (dLGN) by using Cholera toxin subunit B as an anterograde tracer. Finally, we investigated the receptive field properties of excitatory neurons in visual cortex (V1) using two-photon calcium imaging at cellular resolution in mice expressing the genetically encoded calcium sensor GCaMP6s. Motor performance was normal in mice receiving early postnatal hypoxia. In contrast, visual acuity was impaired on average and highly variable in hypoxic mice and a subset of hypoxic mice was unable to perform the task reliably. Binocular depth perception was also impaired by early postnatal hypoxia. On average, the pattern of eye specific segregation was largely unaltered in early postnatal hypoxic mice. However, there is greater variability in the segregation of ipsilateral and contralateral retinal projections in hypoxic mice. The orientation and spatial frequency tuning of visual cortical neurons were unaltered in the perinatal hypoxic mice. The ocular dominance of the hypoxic mice also resembled normoxic mice. These visual behavioral deficits resemble facets of human CVI. The establishment of an early postnatal hypoxic mouse model of CVI will provide a foundation for both characterizing this prominent visual disorder and developing rational treatment options.
Recommended Citation
Oakes, Dana K., "Establishing a mouse model of cerebral/cortical visual impairment." (2024). Electronic Theses and Dissertations. Paper 4444.
Retrieved from https://ir.library.louisville.edu/etd/4444
