Torsten Wiesel - US grants

The objective of this study is to clarify the mechanisms responsible for the genesis of myopia and to develop procedures to prevent this condition. We have shown that surgical lid fusion in neonatal macaque monkeys causes an axial length myopia that is very similar to the human refractive error. In the rhesus macaque, elongation of the eye is primarily caused by disruption of the control of eye growth that is exerted by the retina. In contrast, eye elongation in the stump-tailed macaque is mainly due to the central nervous system through excessive accommodation. The application is concerned with (a) identification of the molecule/s released by the retina that modulate eye growth in the rhesus macaque and testing their effects both in vivo and in vitro; (b) inducing myopia in stump-tailed macaques by forcing the animal to accommodate through behavioral control; (c) assessing the relative contribution of the retina and central nervous system to the pathogenesis of lid-suture myopia in these two primate species.

vision; computer system design /evaluation; visual photoreceptor; computers; computer graphics /printing;

The group in vision research proposed to be supported by this core grant has functioned as a unit for over 10 years. Our group consists of a group of investigators centered at The Rockefeller University, and including investigators from the departments of anatomy and ophthalmology at Cornell University Medical College. The program in vision research includes studies in molecular and cellular neuroscience, in development and in the integrative functions of the visual system. The purpose of this core grant is to foster collaboration among the members of the group, and to provide continued support of common facilities. The core consists of the following modules: 1) computers and computer graphics, 2) histology and electron microscopy, 3) photograph and 4) tissue culture and hybridoma technology. In addition there is a module to administrate the core facilities. These facilities are necessary for the investigators to carry out the projects for which they have been funded through their R01 grants. It has been possible to build up this unit over the last 5 years because of the availability of a Javits Center of Excellence grant, but this program is to be eliminated in 1990 and therefore not subject to renewal. Thus this grant, which will replace the Javits grant, is essential for the support of the existing shared facilities in the laboratory, making possible the continuance of the research pursued by the investigators included in the proposal and the further growth of vision research at this center.

This U.S.-Brazil Cooperative Research award supports cooperative research in developmental neurobiology to be conducted by Dr. Torsten Wiesel and Dr. David Sretavan of Rockefeller University and Dr. Ary Ramoa of the Federal University of Rio de Janeiro, Brazil. The goal of this research is to understand how precise patterns of axonal projections, present in the mature mammalian visual system, are established during development. The experiments will focus on three areas. First, is the nature of the cellular interactions between developing retinal axons and neuro- epithelial cells at the optic chiasm. Second, is the identity and spatial-temporal distribution of cell surface molecules present on both retinal axons and neuroepithelial cells. Third, is the further development and refinement of an in vitro culture system to study retinal ganglion cell axon pathfinding. Results from this set of studies will not only lead to a better understanding of how a major axon pathway in the visual system is formed during embryonic development, but will also provide insight into how specific axonal projections may arise in other parts of the central nervous system. Dr. Ramoa will bring to this project his expertise on the embryonic development of mammalian retinal ganglion cells and will also benefit by learning a powerful research technique which will be of direct use in his own research in Brazil. Dr. Ramoa's past research has focused on the development of mammalian retinal ganglion cells in terms of the maturation of their morphological features and their electrophysio- logical properties. While in the U.S., Dr. Ramoa will work with Dr. David Sretavan using hybridoma techniques to generate monoclonal antibodies directed against molecules present on developing retinal ganglion cells and the neuroepithelial cells of the optic chiasm.

biomedical equipment purchase;

The goal is to understand the cellular basis of vision, including the development of the visual system and the role of genetic and environmental factors. The studies will include the analysis of the neural circuitry of the cat and moneky striate cortex using the method of intracellular recording and staining with horse radish peroxidase (HRP). Of special interest is to learn more about the intrinsic horizontal connections and their part in shaping local and global response properties of cortical cells. The functional importance of a given connection will be tested by reversible blocks of a given pathway using local GABA injection. In vitro slices of the striate cortex from cats and monkeys will also be used in studies of circuitry. Specific cell types, retrogradely labelled by injection of fluorescent beads at their site of projection, can be visualized in the living slice for intracellular staining with Lucifer yellow or HRP. The development of specific intracortical connections, such as the clustered horizontal connections, will be studied in kittens of different ages, raised under normal or visually deprived conditions. Color, direction of movement, depth and pattern vision appears to be processed by higher centers through segregated projections to different cortical areas. These projections will be studied in the monkey using single cell staining and reconstruction in combination with histochemical methods. Functional connections between cells in the visual cortex will be studied by correlating the activity of two simultaneously recorded cells. This methods makes it possible to examine the specificity of neural connections with reference to the laminar, columnar and clustered nature of the cortical architecture. The method will be further developed to include an array of up to 32 electrodes for simultaneous recording of many cells, the activity of which will be correlated on line. The correlation between cortical cells can vary with stimulus conditions and the multielectrode array will make it possible to analyze the dynamic neural connections within a small cortical area and perhaps between cortical areas. Another approach to the study of the functional architecture, which has been developed in the laboratory, is an optical recording method. The regional distribution of cortical activity will be examined under different stimulus conditions in both the cat and monkey and related to the response properties of single cells.

Cuenod 9320139 This award will support the 1993 activities of the Human Frontier Science Program (HFSP), an international, non-governmental organization located in Strasbourg, France and dedicated to supporting international collaborative basic research and long-term (two-year) post-doctoral fellowships in the elucidation of brain functions and molecular biology. The HFSP was originally proposed by the Government of Japan in 1987 at the Venice Economic Summit of the leaders of the major Western countries. The participating countries include Canada, France, Germany, Italy, Japan, Switzerland, the United Kingdom, the United States, and the European Community. In 1993 the HFSP awarded 42 research grants and 152 two-year, post-doctoral fellowships. Sixteen grants and fifteen post-doctoral fellowships were awarded to American researchers. In addition, 95 fellowships were awarded to foreign post-docs who expressed the intention to conduct their research in the United States. The U.S. contribution of $3.5 million includes funds provided by the National Science Foundation, the National Institutes of Health, the Department of Energy, and the National Aeronautics and Space Administration.

The group in vision research proposed to be supported by this core grant has functioned as a unit for over 10 years. Our group consists of a group of investigators centered at The Rockefeller University, and including investigators from the departments of anatomy and ophthalmology at Cornell University Medical College. The program in vision research includes studies in molecular and cellular neuroscience, in development and in the integrative functions of the visual system. The purpose of this core grant is to foster collaboration among the members of the group, and to provide continued support of common facilities. The core consists of the following modules: 1) computers and computer graphics, 2) histology and electron microscopy, 3) photograph and 4) tissue culture and hybridoma technology. In addition there is a module to administrate the core facilities. These facilities are necessary for the investigators to carry out the projects for which they have been funded through their R01 grants. It has been possible to build up this unit over the last 5 years because of the availability of a Javits Center of Excellence grant, but this program is to be eliminated in 1990 and therefore not subject to renewal. Thus this grant, which will replace the Javits grant, is essential for the support of the existing shared facilities in the laboratory, making possible the continuance of the research pursued by the investigators included in the proposal and the further growth of vision research at this center.