Studies on Endogenous Neurogenesis in the Adult Mammalian Substantia Nigra

We have published evidence for a slow, endogenous generation of new dopaminergic nerve cells in the adult mouse midbrain, i.e. the nerve cell type lost in Parkinson's disease. (PNAS 100, 7925-7930, 2003). In this project, we will further explore our new hypothesis that there is a neuronal turnover in the adult midbrain. In theory, at least some clinical manifestations of Parkinson's disease could be caused by an imbalance between newborn and dying dopaminergic nerve cells, i.e. a too slow generation of new neurons in relation to the neuronal loss, leading to a gradually developing net loss of nerve cells. We will explore these theories in vivo by incorporating markers for newly generated cells in a recently identified population of adult neural stem cells and immature progenitor cells in the midbrain. We will follow this cell population as it approaches and enters substantia nigra in a slow migratory flow of new-born cells that ultimately differentiate into fully developed dopamine neurons sending out nerve terminals to the appropriate targets and integrating into known brain circuits.