These studies have involved a diverse range of cellular models including cortical neurons from freshwater turtles, neural progenitor cells from Arctic ground squirrels and isolated cortical neurons from sea lions and elephant seals. We are primarily interested in the signaling pathways that exit in neurons that enable the cell to respond to hypoxia with an adaptive response that makes the cell more tolerant to subsequent severe hypoxic stress. The current model involves human neurons, derived from a neural progenitor cell line, and signaling pathways of the unfolded protein response (UPR), a system that regulates response to a wide variety of stresses. The UPR is a key player in preconditioning.