Title

Midbrain Dopamine Neurons and Adult Neurogenesis

Date of Completion

January 2012

Keywords

Biology, Neuroscience|Biology, Cell|Biology, Neurobiology

Degree

Ph.D.

Abstract

The subventricular zone is a region within the adult brain that harbors stem cells capable of producing new neurons throughout adulthood. The factors that regulate adult neurogenesis in the SVZ, and the factors critical for the maintenance of the SVZ stem cell niche throughout aging have not been completely described. Here, two factors that may play a role in the regulation of the SVZ in the adult and aging mammalian brain were analyzed: midbrain dopamine signaling, and the ependymal monolayer of the SVZ. ^ One candidate SVZ-regulatory molecule is the neurotransmitter dopamine; however, the role and origin of dopamine signaling in the SVZ is not fully known. In order to further elucidate the role of dopamine signaling in the SVZ we used pharmacological and genetic mouse models, and found that dopamine afferents that innervate the SVZ originate in the ventral tegmental area of the midbrain. These findings suggest that neurogenesis in the SVZ may be regulated in part by signaling from a region of the brain typically associated with motivation and reward processing. ^ Another potential regulatory component of the SVZ niche is the ependyma, a monolayer of cells that create a barrier between the SVZ and the cerebral spinal fluid- filled lateral ventricles. In order to further understand the relationship between the SVZ and the ependymal cell barrier we used magnetic resonance image data sets to evaluate the spatiotemporal expansion trends in the lateral ventricle. Here, we describe a unique method to characterize the changes that occur in the SVZ-ependymal bather region through aging. Together, this work increases our understanding of the SVZ, and the factors required for SVZ-mediated neurogenesis in the adult and aging brain. ^