(from abstract): We seek support to continue studies of the development of aspects of visual system organization that are highly evolved and unique to primates. For this reason we have selected an Old World primate, the macaque monkey, that possesses parallel color-opponent or parvocellular (P) and broad-band or magnocellular (M) pathways with ratios of M and P cells that are similar to human at the level of the retina, the lateral geniculate nucleus (LGN) and the visual cortex. This primate-specific segregation of the visual system into functional domains emerges in development as result of intrinsic and extrinsic factors operating at each stage. Our working hypothesis is that at early stages of development, intrinsic mechanisms predominate within the retina, LGN and cortex while at later stages, largely extrinsic, reciprocal interactions between the visual centers orchestrate the development of the compartmental architecture of the primate visual system. Our goal is to determine when and how the circuitry of M and P streams becomes coordinated from the periphery (retina) to the center (cortex) and to uncover genes that may be involved in this process at each level, during both the early and late phases of development. We will manipulate the relative size of M and P streams either by deleting afferent input from retina by prenatal surgery or by selectively reducing various classes of target neurons by timed X-irradiation in the primate embryo and will then examine the consequences of these manipulations on the mature system. We will also identify and characterize gene products that are expressed in the prospective striate and extrastriate cortex in embryos prior to and upon its innervation from the thalamus. The issues addressed in this grant will require a battery of methods including: immuno- and histochemistry, in vitro autoradiography, in situ hybridization, optical imaging and antero and retrograde axonal tracers, applied to either normal embryos or mature animals with altered visual systems. These experiments are designed so that each animal will supply tissue for multiple purposes, thus providing both correlative developmental data as well as maximizing the amount of information obtained.
The aim of these studies is the elucidation of the timing, sequence and mechanisms that govern both normal and altered development of vision in primates as a basis for the understanding of normal and abnormal vision in humans.
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