Mechanisms of Developmental Plasticity in the Mammalian Olfactory System

Case Western Reserve University, Cleveland OH

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Abstract

Project Summary/Abstract. In the mammalian nervous system, a heightened level of plasticity is observed during early postnatal development that enables the neural circuit to change according to environmental stimuli. We have discovered that the mammalian olfactory sensory neurons (OSNs) undergoes a developmental switch during a critical period of development. OSNs born during the perinatal period exhibit high levels of plasticity, exuberant axon growth, and can alter their innervation targets following prolonged odor stimulation. Neurons born after the critical period no longer exhibit these characteristics. The objective of this application is to determine the molecular control of the critical period in olfactory system development. In particular, we will study the role of Fzd1, which have multiple functions in regulating cellular and developmental processes in neural and non- neuronal tissues, in regulating the critical period. By combining genetic manipulation, transcriptome analyses, protein interaction assays, imaging, and behavioral assays, we will determine the requirement of Fzd1 in regulating developmental plasticity of the OSNs. We will further determine at the molecular level how Fzd1 interact with other partners to increase neuronal plasticity during early phase of development and how it regulates a transcriptional program to close the critical period. These studies will provide mechanistic insights into axon pathfinding during OSN development and during adult neurogenesis.