We are exploring the roles of PKA and localized signaling complexes in neural networks using mouse genetics and viral approaches. The mouse allows a full complement of genetic manipulations and in most instances provides a relevant model of human physiology, behavior, and disease. We are focused on two areas of interest: the involvement of cAMP/PKA in the regulation of energy metabolism and the role of localized PKA in the hippocampus. In the hypothalamus, PKA activity modulates the sensitivity of neurons to leptin and controls feeding and energy expenditure. In the hippocampus we have found that presynaptic PKA localized by an AKAP regulates synaptic plasticity in the dentate granule cells and controls contextual discrimination at a behavioral level. We have developed techniques for isolating the translated mRNA population from specific subsets of neurons using ribosome tagging (RiboTag) and use this technique to examine changes in mRNA expression and translation as neurons respond to hormones and physiological stimuli.
Copyright © 2003-2014 Molecular & Cellular Biology Program, University of Washington
Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research