Arthur G. Shapiro - US grants

neural information processing; electroretinography; cone cell; visual photoreceptor; psychophysics; electrophysiology; noninvasive diagnosis; human subject;

Amblyopia (commonly known as "lazy eye" Or literally as "blunt sight") is a condition in which vision in one eye is poor even though any refractive error is corrected and there is no other obvious damage to the eye. It is now widely accepted that the clinical pathology in amblyopia involves a functional weakening of connections between the visual cortex and one or both of the eyes. The condition affects about 3% of the general population and arises during childhood while the visual centers of the brain are still developing. It is an almost certain outcome of anything that causes the two eyes to see differently during infancy or early childhood, such as an uncorrected strabismus, cataract, or anisometropia. Current treatments are helpful if performed early enough, but beyond 7 or 8 years of the age the condition is untreatable. The long-term objectives of this project are l) to provide a possible route for growth factor therapy of amblyopia in adulthood, and 2) to further understand mechanisms underlying actions of nerve growth factor (NGF) in visual cortex plasticity. 0ne specific aim of this proposal is to undertake efforts to promote recovery from pre-existing amblyopia in experimental animals with NGF-treatment. Amblyopia will be induced artificially in young kittens by suturing shut the eyelid of one eye. The animals will be allowed to grow up in this situation. It is already known that this will result in the sutured eye losing functional connections with the visual cortex. 0nce these animals are past the critical period for visual cortex plasticity (at least one year of age), NGF will be infused into the visual cortex coincident with manipulations of visual inputs through the two eyes. Then ocular dominance distributions of neurons will be assessed in both NGF-treated and control visual cortices with standard single unit recordings. Another specific aim of this proposal is to investigate whether NGF-induced plasticity in adult visual cortex is mediated through the cholinergic pathway. Antagonists of cholinergic receptors will be infused with NGF, together into visual cortex of adult cats, and the effects of NGF on ocular dominance distributions of visual cortical neurons will be determined using electrophysiological recordings.

DESCRIPTION (provided by applicant): Our ability to see color has long been a central issue for vision research. Color vision is important for most people's quality of life, and the deterioration of color vision often indicates serious health-related vision problems. Color, however, is a complex perception that depends not only on the wavelength of a light, but also on the context in which the light is presented: for example, for an observer with no color vision deficits, a white disk looks green when surrounded by a red ring. Explanations for the effects of context typically posit that the neural response to the target light (in this case, the white disk) is modified by the neural response to the contextual light (in this case, the red ring). Such explanations have been valuable for understanding many aspects of the visual brain but generally do not attempt to account for the fact that objects can be described in terms of both their color and their color contrast (a red disk surrounded by a white ring appears "red with high contrast," but a red disk surrounded by a pink ring appears "red with low contrast"). Over the past few years, the Shapiro laboratory has developed new techniques to show that the visual response to color contrast can be measured separately from the visual response to color. The results have led to the development of a computational model in which the visual system carries two different classes of signal: a signed (or non-rectified) response that corresponds to the neural channels typically studied in color vision experiments, and an unsigned (or rectified) response that encodes color contrast. The experiments described in Specific Aims 1 and 2 use the temporal and spatial signatures of the rectified and non-rectified responses to understand fundamental characteristics of those responses at threshold and super-threshold levels. The experiments described in Specific Aim 3 examine a ramification of the model, with respect to brightness perception: i.e., the hypothesis that the parts of the human visual system that encode brightness act like an adaptive high-pass filter that removes low spatial frequency content from the visual scene, with the cutoff frequency determined by the image content. My proposed model is of interest to many Vision Science researchers. Specific aim 4 shows specific collaborations that have clinical applications that can be developed as a consequence of this R15 award. PUBLIC HEALTH RELEVANCE: Color vision is important for most people's quality of life, and the deterioration of color vision often indicates serious health-related vision problems. The research in this proposal seeks to understand aspects of color vision related to a model that proposes separable neural processes for color and color contrast, developed by Shapiro (2008). The techniques described in this proposal are new and can be applied to the study of Congenital Stationary Night Blindness, and visual decline that occurs as a result of aging.