InvestigatorVan A. Doze, Ph.D.

Location:  Department of Biomedical Sciences, University of North Dakota

Title:  Noradrenergic regulation of neurogenesis and cognitive function

Description:  NE Norepinephrine (NE), an important neuromodulator in the brain, modulates cognitive function and synaptic plasticity, which is thought to underlie learning and memory.  NE mediates its effects through the activation of adrenergic receptors (ARs).  We discovered that adult mice with chronically activated alpha1A-ARs exhibit significantly improved cognitive functions, synaptic plasticity, mood, and lifespan.  These mice also show increased neurogenesis in their hippocampi, an area of the brain critical for learning and memory.  The molecular cues and genes regulating this process include a wide range of growth and survival factors, but a direct link between NE activity, gene regulation, and neurogenesis, has not been explored.  This project will test the hypothesis that NE, through alpha1A-AR activation regulates differentiation and cell fate of neuronal and glial progenitors in the adult mouse brain, and subsequently enhances cognitive function.  This project will examine gene expression in the hippocampi and brain of mice with chronically activated alpha1A-ARs.  The global gene expression between treated and untreated mice will be compared and the significant differentiation in genes and signal pathways identified.  Change in expression for selected genes will be verified using real-time PCR.  Through immunolabeling, electrophysiology, and confocal imaging, this project will characterize alpha1A-AR influences on cell migration, differentiation, fate/survival and function.  This research study will increase our understanding of the role of NE in adult neurogenesis and learning.