In humans each eye makes specific and complementary connections with populations of neurons on both sides of the brain. More than half of all fibers that grow out from the retina form a crossed projection that connects with target neurons on the other side of the brain. The reminder form an uncrossed projection that connects with targets on the same side. Establishing this specific pattern of connections is an absolute prerequisite for normal vision. Inborn errors of these connections are associated with poor foveal development, severe deficits in visual acuity, loss of binocular vision, strabismus, and eye movement disorders. For these reasons it is critical to know more about the mechanisms responsible for generating precise neuronal connections. It is also important to understand the degree of functional adaptation that individuals with inborn errors of connection may be able to make. These issues are addressed in this project, which takes advantage of a remarkable mutation carried in sheepdogs. In mutant animals, the entire retinal projection is usually misdirected into the ipsilateral (uncrossed) optic tract. A similar, if not identical, syndrome has recently been discovered in humans. In dogs, and probably in humans, the aberrant connection causes highly abnormal visual maps in the dorsal lateral geniculate nucleus. And in both dogs and humans, the aberrant connection is also consistently associated with a pronounced and persistent eye movement disorder referred to as congenital nystagmus. An important reason to study this mutation is that it provides us with a unique system in which to test many current ideas about the formation of topographic representations in the CNS. In particular, the mutation provides a superb model with which to validate, reject, or modify hypotheses about the role of axon-target interactions, nasal-temporal rivalry, and binocular competition in partitioning visual nuclei and the visual cortex into sets of visuotopic representations. We will use physiological recording methods and complementary tract tracing methods to determine the functional and structural repercussions that result from the drastic decussation error. In specific, we will determine how nasal and temporal projections that originate from the same retina organize themselves in the visual cortex and in the superior colliculus of mutants. This systematic analysis of retinotopy in mutants will provide us with a way to assess the plasticity of visual maps and will also provide us a way to critically test several important hypotheses regarding the formation of topographic representations. In summary, the achiasmatic mutant provides us with a powerful means to test influential ideas regarding the development, function, and plasticity of the vertebrate visual system. In addition, this mutation shows great promise as an animal model for congenital nystagmus in humans. The mutants may ultimately help us in developing and testing new methods to treat oculomotor disturbances in humans.
| Williams, R W; Rakic, P (1988) Elimination of neurons from the rhesus monkey's lateral geniculate nucleus during development. J Comp Neurol 272:424-36 |
| Williams, R W; Rakic, P (1988) Three-dimensional counting: an accurate and direct method to estimate numbers of cells in sectioned material. J Comp Neurol 278:344-52 |
