Norberto Grzywacz - US grants

Visual detection of motion occurs via neurons that selectively respond to the direction of movement in the visual field. Cells in the retinal ganglia give ON/OFF responses when moving objects cross their receptive fields in appropriate directions. This implies that there are neural circuits that inhibit the responses of these cells, and it is those circuits that are the object of investigation in this project. The study addresses four major questions: 1. Are these cells essential to direction selectivity or do they simply function in determining velocity and orientation? 2. How does the inhibition interact with excitation in the retina? 3. How does the inhibition relate to the cells' tuning to velocity and direction selectivity? 4. How dependent is the inhibition on the contrast of the object whose motion is being perceived? The methods employed include electrophysiology, pharmacology and immunohistochemistry, with computational theoretical analysis of the data. The work is significant for a number of reasons. It includes analysis of general mechanisms that are probably fundamental to the function of the brain. It will also demonstrate the limitations of early motion measurements, perhaps setting constraints on what may be expected of motion perception. Finally, it includes the development of new experimental as well as theoretical tools that will be applicable to studies of motion perception mechanisms in higher centers of the brain. *** //

DESCRIPTION (From the Applicant's Abstract): A central problem in visual neuroscience is the binding problem. How does the brain know that it has to bind the responses of neurons with small visual windows to obtain coherent pictures of large objects? One long-term goal of the proposed research is to elucidate the retinal mechanisms underlying visual binding. Three hypotheses for these mechanisms involve gap junctions between ganglion cells, and common cholinergic, glutamatergic, and GABAergic synapses. Four specific aims will test these hypotheses in directionally selective ganglion cells of turtles and rabbits, since evidence of long-contour binding exists for these cells: 1)This aim will test whether millisecond correlation could code long, moving contours by recording simultaneously from neighbor directionally sensitive cells with electrophysiological techniques. 2)The experiments here will use simultaneous electrophysiological recordings and pharmacology to test the GABA, acetylcholine, glutamate, and gap-junction hypotheses of retinal correlation. 3)Specific aim 3 will study whether long-range correlation takes place by mapping the population of directionally selective cells with live Ca2+fluorescence. 4)Finally, the last aim will test a prediction of the cholinergic hypothesis for correlation by measuring acetylcholine release following motion adaptation with high performance liquid chromatography. The study of binding may have important health relevance. Schizophrenia patients, for instance, cannot detect contours in tasks relying on long-range spatial interactions of orientational signals. And the integration of orientation information across space is impaired in amblyopia. Retinal binding defects may contribute to some of these integrative problems, but even if not, retinal strategies and mechanisms may shed light on mechanisms in other areas of the brain.

DESCRIPTION (provided by applicant): An important property of visual neurons is their receptive-field size. One long-term goal of the proposed research is to understand the developmental mechanisms controlling the growth of retinal receptive fields. We recently established that one such mechanism depends on the spontaneous waves of activity that sweep developing retinas. Four hypotheses for this mechanism involve dendritic-tree growth, optimization of receptive-field size, critical period for growth, and inter-cell competition. We will test these hypotheses in the turtle retina with four aims: 1) We will use intracellular recordings and dendritic staining to test whether spontaneous waves cause receptive fields of ganglion cells to grow by enlarging their dendritic trees. 2) Turtles will be reared in abnormal light environments to test through extracellular recordings whether receptive fields grow to a size optimized to average out noise, while not over-smoothing the image. 3) Ca2+ fluorescence will help us map the waves and ask how light affects them. 4) We will test whether receptive-field growth stops because of a critical period or of an inter-cell competition by increasing the intensity of dark-reared waves though the retinal implantation of drug-laced Elvax. This study could help understand several developmental pathologies affecting ganglion cells. These pathologies include retinopathy of prematurity, retinal degeneration, refsum disease, Leber hereditary optic neuropathy, optic-nerve hypoplasia, and drusen of the optic disk. Besides understanding pathologies, unraveling ganglion-cell plasticity may help with a promising technique for one of their cures, namely, retinal transplantation. In such a transplantation, cells must "self-organize" as during development.

DESCRIPTION (provided by applicant): Low vision is a significant reduction of visual function that cannot be fully corrected by ordinary lenses, medical treatment, or surgery. Aging, injuries, and diseases can cause low vision. Its leading causes and those of blindness, include cataracts and age-related macular degeneration (AMD), both of which are more prevalent in the elderly population. Our overarching goal is to develop devices to aid people with low vision. We propose to use techniques of computer vision and computational neuroscience to build systems that enhance natural images. We plan test these systems on normal people and visually impaired older adults, with and without AMD. We have three milestones to reach: 1) Our first milestone will be to develop a system for low-noise image-contrast enhancement, which should help with AMD, because it causes lower contrast sensitivity. 2) Our second milestone will be a system that extracts the main contours of images in a cortical-like manner. Superimposing these contours on images should help with contrast-sensitivity problems at occlusion boundaries. Diffusing regions inside contours should help with crowding problems prominent in AMD. 3) Our third milestone is to probe whether these systems can help people with low vision people. For this purpose, we plan to use a battery of search and recognition psychophysical tests tailor-made for AMD. We put together an interdisciplinary team. The Principal Investigator is Dr. Norberto Grzywacz from Biomedical Engineering at USC. Drs. Gerard Medioni from Computer Science and Bartlett Mel from Biomedical Engineering at USC will lead the efforts in Specific Aims 1 and 2 respectively. Drs. Bosco Tjan from USC Psychology, Susana Chung from the University of Houston, and Eli Peli from Harvard Medical School will lead Specific Aim 3. Other scientists are from USC. They include Dr. Irving Biederman from Psychology, an object-recognition expert and Dr. Mark Humayun, from Ophthalmology, an AMD expert. They also include Dr. lone Fine, from Ophthalmology, an expert in people who recover vision after a prolonged period without it and Dr. Zhong-Lin Lu, an expert on motion perception and perceptual learning.

The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP institution.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.