Lawrence E. Mays - US grants

DESCRIPTION (Investigator's Abstract): The vergence eye movement system adjusts the angle between the eyes during shifts in gaze between far and near objects. This system is primarily responsible for the normal alignment of the visual axes during binocular viewing. Although misalignment of the eyes is the most common human oculomotor complaint, the normal function of the neural circuits which control vergence is only now becoming understood. The overall aim of this project is a comprehensive understanding of the neural circuits which control vergence eye movements. This goal is approached in a series of experiments using electrophysiological recordings from the brains of alert, behaving monkeys. The animals are trained to maintain precise ocular fixation and make conjugate and vergence eye movements on demand. The position of both eyes is measured using an accurate search coil technique. Because the vergence system works in conjunction with brain circuits which adjust the dioptric power of the lens, procedures for controlling and measuring lens accommodation are also used. In most of the experiments, single unit recording is used to determine the signals carried by individual neurons in the midbrain and pons. In some experiments, the technique of antidromic activation is used to identify cells which project to the motor nuclei. The accurate measurement of responses, together with sophisticated behavioral paradigms, allows a precise, quantitative analysis of neuronal signals. The aim of the first series of experiments is to identify midbrain and pontine neurons which project to the extraocular motor nuclei and determine the conjugate and vergence signals they carry. Previous work has shown hat such signals cannot always be inferred form the anatomical connections of the cells which carry them. Another experiment will test a recently proposed model of accommodation and vergence interactions at the neuronal level, using an adaptation paradigm. A final experiment will test the hypothesis that the saccadic and vergence systems are independent. This will be done by determining how vergence and saccadic velocity commands are combined at the level of the motoneurons.

biomedical equipment resource; biomedical equipment purchase;

This application is for continued core support of a Vision Science Research Center located in the School of Optometry, University of Alabama in Birmingham. The requested funds would provide support personnel, equipment, and supplies for five research support modules shared by a group of twenty-one vision scientists. The support modules are I-Center Administration, II-Electronics, III-Tissue Processing Module, IV-Data Management and Analysis (Computer), and V-Illustration and Graphics. Fourteen of the participants in the center have faculty appointments in either the Department of Physiological Optics or the Department of Optometry, both in the School of Optometry. The remaining seven participants have faculty appointments in either the Departments of Anatomy, Chemistry, Pharmacology, Physiology, or Psychology. The center is an administrative subunit of the Department of Physiological Optics and the Center Director, along with the four Module Directors, are responsible for the administration of the Center's activities. The major research focus of the center is neurobiology, with almost half of the Center's participants actively involved in anatomical, physiological, and psychophysical studies of the visual system. Other areas of emphasis are corneal biochemistry and physiology, ocular pharmacology, photochemistry, epidemiology of refractive error, and visual optics. In addition to the existing CORE support, the continued development and growth of the Vision Research Center is supported by faculty salaries from the various departments involved, and by research support services, equipment and facilities provided by individual departments and the university as a whole. The continued CORE support requested in this application provides shared resources not available through other funding mechanisms. These shared facilities increase the efficiency and productivity of research efforts on individually funded projects, afford participants more flexibility in taking new research directions, and promote more collaborative research among a group having multidisciplinary approaches to vision science.

The initial award of a CORE grant for vision research in 1979 began a period of remarkable expansion of the multidisciplinary UAB Vision Science Research Center. From that time, the vision CORE has expanded from 13 researchers with primary appointments in 2 departments to a group of 25 researchers with appointments spread over 9 different departments. The total funding to individual researchers for vision science has increased from $0.7M to $2.4M. In part due to the success of the CORE, the School of Optometry and the University purchased a free-standing building of 21 ,000 sq. ft. to serve as the Vision Science Research Center. This building, only three blocks from the center of campus, has given vision science a position of prominence on the UAB campus. It is easily accessible to all CORE participants. We note that all NEI funded investigators on the campus are active CORE participants. This competing renewal seeks to continue the support of vision scientists at UAB by providing shared services to principal investigators which are not available to them through their individual research grants. The shared services are provided by four CORE modules. These modules provide accessible technical facilities in dedicated CORE laboratories designed specifically for vision science. Importantly, CORE-supported personnel provide human expertise which is not available elsewhere. In the Electronics Module an electronics equipment engineer designs and fabricates new electronic apparatus and provides vital emergency repair and maintenance services. In the Computer Module a programmer helps configure computers and customize software, thus easing the difficulties individual investigators can experience in using computers productively in research. In the Histological Analysis Module an experienced histology technician provides help and expertise in histologic and immunohistochemical techniques, and maintains a productive research environment in which investigators can interact. In the Biostatistics Module a faculty level biostatistician provides collaboration, consultation and instruction on statistical issues related to individual clinical and basic vision research problems. Together these modules enhance the capability and efficiency of individual investigators and facilitate collaborative studies.

vision; computer center; biomedical facility;

ABSTRACT

A grant has been awarded to Dr. Gamlin at the University of Alabama at Birmingham (UAB) to acquire a state-of-the-art vertical, 4.7 Tesla, magnetic resonance imaging (MRI) device designed especially for use with alert, trained non-human primates. MRI, especially functional MRI, is an exciting new tool that is revolutionizing our ability to study the brain. However, this technology has limitations when applied solely to humans. A major limitation is that once a brain region is identified by fMRI as being functionally activated during a specific task, additional invasive, experimental options are limited. However, by using non-human primates, further studies are not limited to imaging alone. One can conduct electrophysiological studies using single- and multi-unit recording, and neuroanatomical and pharmacological inactivation techniques to significantly enhance the level of understanding of brain function. Therefore, this 4.7T MRI system will be used in a primate Neuroimaging Facility which, when combined with existing neurophysiological techniques, will be able to examine brain function at both microscopic and macroscopic scales and with temporal resolutions of milliseconds - experiments that are not currently feasible in humans. In addition, using this combination of techniques, new pulse sequences will be developed and validated to ensure that fMRI images more accurately reflect the spatial and temporal characteristics of the underlying neural activity.
UAB has assembled a group of internationally-recognized neuroscientists with expertise in studying the underlying mechanisms of visual, sensorimotor, and oculomotor processing in alert, behaving primates. The primate visual system is the most extensively studied primate sensory system and the oculomotor system is the best understood primate motor system. Thus, these UAB investigators are in a unique position to fully exploit fMRI techniques to better understand the behavior of these model neural systems and, in so doing, contribute to a deeper understanding of brain function in general. The planned research projects will include the investigation of neural mechanisms related to vision, eye movements, plasticity, and sensorimotor integration in occipital, parietal, temporal, and frontal cortex. Other projects will involve the development of better functional and spectroscopic MRI techniques.
The planned Neuroimaging Facility, which will be one of only a few facilities in the world in which research spanning single neurons to whole brain behavior can be conducted in the same research animal, will be developed into a regional/national resource for research in Neuroscience. This planned facility thus has the potential to make major contributions to the field of functional brain research. The planned Neuroimaging Facility will have a major impact on recruitment and training of students in this emerging research area. Specifically, to ensure that the next generation of scientists will exploit this resource fully and develop MRI techniques further, participating faculty will ensure that students are trained in-depth in both neuroscience and MRI imaging. Further, UAB's Comprehensive Minority Faculty and Student Development Program, the NSF-funded Alliance for Minority Participation, and the Alliance for Graduate Education and the Professoriate Program, will ensure that a significant proportion of these students are from underrepresented groups.