In the visual system, the eye receives stimuli from the outside world and transfers information to multiple areas in the brain, where the bulk of visual processing occurs. Neurons in the eye synapse with their targets with precisely defined spatial order. This order is thought to be crucial for correct functioning, and has two organizing features. Each eye's connections to the brain are arranged topographically, meaning that the nearest neighbor relationships of eye neurons are pre-served in their connections. In addition, visual input from both eyes are aligned in the brain in the form of eye-specific layers. The purpose of this proposal is to further our understanding of the generation of precise neural connectivity. We are taking a genetic approach, combined with classical axonal tracing techniques, to dissect the role of genetic determinants in the generation of ordered visual maps. We are primarily focusing our effort on determining the functional requirements of the Eph family of receptor tyrosine kinases and their ligands, ephrins, in primary visual map formation. Recent work has shown that ephrin-mutant mice have defects in the mapping of retinal axons to both the superior colliculus and the lateral geniculate nucleus. The nature of these defects lead to the hypothesis that ephrins are important for both topographic mapping and eye-specific layer formation. We propose to test this by characterizing the visual projections in ephrin-mutant mice and correlating the mapping defects in with ephrin expression patterns in the developing visual system. The formation of precise neuronal connections is strictly required for productive communication between neurons. Understanding the basic processes that specify proper connectivity in the visual system will be directly relevant to neurological disorders involving aberrant neuronal connections and processing, such as, generalized seizures, sleep disorders and mental retardation. These studies are expected to contribute to our understanding of the mechanism by which visual information is transferred from one brain region to another. The mechanisms are most likely shared with those required for the regeneration of axonal connections after damage due to injury or disease.
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