J-661F, Magnuson Health Sciences Center
Our laboratory uses molecular genetics techniques to characterize neuronal circuits that regulate feeding and other behaviors in the mouse. We are particularly interested in neurons in the arcuate region of the hypothalamus that express agouti-related protein (AgRP) and neurons in the parabrachial nucleus (PBN) that express calcitonin gene-related protein (CGRP). We start by targeting Cre recombinase to neurons of interest in embryonic stem cells and then use genetic crosses or viruses to express Cre-dependent effortor genes (e.g. fluorescent proteins, channelrhodopsin, archearhodopsin, Designer GPCRs (DREADDs), Ribo-Tag, Toxins, etc) in those cells. For example, CNO activation of DREADD receptor coupled to Gq or photoactivation of channelrhodopsin in AgRP-expressing neurons promotes robust feeding by mice that were otherwise not hungry. The next step for extending the circuit is to identify relevant target neurons that are influenced by AgRP neuron signaling. As another example, activation of CGRP-expressing neurons that that reside in PBN inhibits feeding by mice that are otherwise hungry. These CGRP-expressing neurons are intermediates in a circuit that begins in the gut and relays visceral information via the vagus to the nucleus tractus solitarius, then to the PBN, and from there to the central nucleus of the amygdala. This anorexia circuit mediates responses to satiety hormones, conditioned taste aversion, visceral malaise and probably many other forms of anorexia. Deciphering the full extent of these orexigenic and anorexigenic circuits and learning how they intersect is a primary focus of the lab.
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Fred Hutchison Cancer Research Center | University of Washington
Institute for Systems Biology | Seattle Biomed