The purpose of this study is to establish an understanding of the molecular mechanisms that underlie neuronal replacement in the adult brain. Assessing the brain's natural ability to repair itself will help determine repair mechanisms to use in situations of neuron loss and degeneration. Recently, neuronal precursor cells which retain the capacity to differentiate into neurons have been found to persist into adulthood. In the mouse, these cells reside in the lateral wall of the lateral ventricles of the brain and migrate to the olfactory bulb where they then differentiate into neurons which function in olfaction. Little is known about these precursor cells: how they remain undetermined in their fate in the otherwise mature and determined structure of the adult brain; or what signals direct their subsequent migration to the olfactory bulb, an even that occurs throughout the lifetime of a mouse. The proposed research will investigate a family of receptors recently found to be associated with the cells of the migratory pathway to the olfactory bulb in adult mice. In other studies, these receptors have been implicated in axonal guidance, as in the developing visual system, and they may be involved in spatial patterning of the early embryo. This is a large and interactive family of receptors, that appear to require cell contact for efficient activation. Initial studies will identify specific family members localized to the migratory pathway. The functional capacity of specific receptors, which are associated with the migrating cells, will be evaluated using in vitro and in vivo assay systems. Studies into the properties of these neuronal precursor cells will provide information about a group of cells that may have tremendous potential int he repopulation of neural tissue that has been damaged by trauma or neurodegeneration.
