Modeling development in retinal afferents: retinotopy, segregation, and ephrinA/EphA mutants.

Abstract

During neural development, neurons extend axons to target areas of the brain. Through processes of growth, branching and retraction these axons establish stereotypic patterns of connectivity. In the visual system, these patterns include retinotopic organization and the segregation of individual axons onto different subsets of target neurons based on the eye of origin (ocular dominance) or receptive field type (ON or OFF). Characteristic disruptions to these patterns occur when neural activity or guidance molecule expression is perturbed. In this paper we present a model that explains how these developmental patterns might emerge as a result of the coordinated growth and retraction of individual axons and synapses responding to position-specific markers, trophic factors and spontaneous neural activity. This model derives from one presented earlier (Godfrey et al., 2009) but which is here extended to account for a wider range of phenomena than previously described. These include ocular dominance and ON-OFF segregation and the results of altered ephrinA and EphA guidance molecule expression. The model takes into account molecular guidance factors, realistic patterns of spontaneous retinal wave activity, trophic molecules, homeostatic mechanisms, axon branching and retraction rules and intra-axonal signaling mechanisms that contribute to the survival of nearby synapses on an axon. We show that, collectively, these mechanisms can account for a wider range of phenomena than previous models of retino-tectal development.