We propose to continue studies of a remarkable mutation of the mammalian visual system in which the entire retinal projection is uncrossed. This drastic inborn error is associated with a marked and persistent nystagmus. A systematic analysis of the visual system of these achiasmatic animals is important for at least two reasons. First, the mutation provides us with a unique natural experiment that is ideal for testing important ideas about the major processes that guide retinal axons at the optic chiasm early in development. We will determine how, when, and why axons fail to cross the midline in mutants. Both light and electron microscopy and several tract tracing methods will be used to perform a systematic structural analysis of the embryonic retina, optic stalk, and chiasm. The analysis should provide insight into the genesis of the norma mammalian chiasm, as well as into the genesis of the severe, decussation error seen in human albinos. This developmental analysis should also provide us with a critical test of the hypothesis that pigmentation controls pathways chosen by retinal axons early in development. The second 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 retinal axons from the same retina organize themselves in two retinorecipient nuclei-the dorsal lateral geniculate nucleus and the superior colliculus. This will be followed by high resolution mapping studies of visuotopic representations in the primary visual cortex 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 |
