The overall objective of this research is to understand the mechanisms responsible for the development of cellular patterns and connections in the nervous system. The development of layers and connections in the lateral geniculate nucleus (LGN) provides an opportune system for investigation of these mechanisms, since the normal system is precisely organized and many aspects of its organization and development are well- documented. Our work on this system has led us to postulate a model that suggests the mechanisms of laminar formation. Each of the specific aims is designed to test aspects of this model in the developing LGN of tree shrews and ferrets.
SPECIFIC AIM 1 will determine whether the developmental sequence of growth of afferents and dendrites supports the idea that these processes interact in a systematic way to produce interlaminar spaces.
SPECIFIC AIM 2 will explore the influence of retinal afferents on LGN cell growth and spacing by: a) blocking axoplasmic transport; b) damaging discrete retinal regions; and c) examining for regional and laminar variations in the ontogenesis of cholinergic processes.
SPECIFIC AIM 3 will examine the influence of developing cortical and collicular projections on interlaminar space formation by: a) deleting these inputs; b) blocking action potentials; and c) monocularly enucleating animals early in development. Finally, SPECIFIC AIM 4 will explore the feasibility of establishing an in vitro model (organotypic culture system) of the LGN to examine the development of cytoarchitecture and connections under controlled conditions. Together, these studies will clarify the mechanism of laminar development in the LGN. These results could, in turn, provide clues concerning the basic rules the produce orderly cellular patterns and connections in the nervous system. These studies are relevant not only to understanding basic mechanisms of normal visual system development, but also to understanding clinical disorders that may affect that development.
