Graduate Training in Neuroscience
University of Washington
G. Stanley McKnight
Professor, Department of Pharmacology
The McKnight lab studies neuronal signal transduction pathways that are regulated by the cAMP/PKA system. One project focuses on the mechanisms that regulate feeding and energy balance in mice using molecular genetic approaches. The cAMP/PKA pathway modulates the sensitivity of neurons in the hypothalamus to leptin and this results in a lean phenotype and resistance to diet-induced obesity. We are trying to define the underlying mechanisms that affect leptin modulated signal transduction and gene expression. A second project involves the role of PKA and PKA anchoring proteins (AKAPs) in hippocampal dentate granule (DG) cells and their mossy fiber projections. The DG cells participate in contextual pattern recognition and mice with a disruption of a presynaptic AKAP that localizes PKA to the mossy fibers exhibit pattern separation deficits and altered mossy fiber LTP. Changes in gene expression in neurons involved in feeding, energy expenditure, or memory and learning are being monitored using a ribosome-tagging strategy (RiboTag) that we developed.
Image of the neurons in the hypothalamus that express the leptin receptor ( red) and the neurons that express the RIIbeta subunit of PKA (green). The image shows the arcuate nucleus at the bottom and the VMH near the top of the picture on either side.