The mission of the National Resource for Aplysia at the University of Miami (the Resource) is to produce and distribute consistently high quality cultured sea hares, Aplysia californica, for biomedical research and education and to improve the usefulness of this model system by applied research. Aplysia have played a vital role in fundamental discoveries of how cellular and molecular changes in the nervous system underlie basic behaviors, learning and memory due to unique characteristics of their simple nervous system that provide an ideal model system for such studies. The two aims of the proposed continuation of this resource program are: 1. Production and Distribution – The Resource will continue to culture A. californica and make all life stages, from eggs to large adults, available to researchers at a reasonable cost. We anticipate sales will continue at a level of 10,000 – 15,000 animals per year. We will also accommodate requests by users for separately reared, same-aged cohorts, specialized diets, or harvesting of specific tissues for RNA or DNA. In addition, we will make available mature and senescent stage animals, validated using criteria generated by the Resource, as well as additional specialized animals as developed in our planned Applied Research programs. 2. Applied Research Programs to support the Resource – We will conduct two applied research projects to create new Aplysia resources that we believe will expand the usefulness of this model system to researchers: 2.1 Molecular characterization of the caloric restriction model of arrested aging – We will investigate the mechanisms involved in lengthening the one year Aplysia lifecycle via caloric restriction (CR). We will document the portions of the life cycle such as pre-reproductive, mature and aged that are prolonged by CR. We will also examine alterations in previously identified gene expression profiles associated with aging at these stages, and determine how they are affected by CR. This project will expand the usefulness of these animals as models of aging. 2.2 Molecular characterization of the hypoxia-resistant nervous system of Aplysia – Hypoxia and ischemia tolerant species have been very useful for understanding the mechanisms by which such animals avoid the catastrophic nervous system damage encountered by humans subject to stroke or similar injuries. Aplysia are very resistant to hypoxia such that their simple, well studied nervous system should be an ideal model for investigating transcriptomic and metabolic adaptations that make this resistance possible. This would create a novel model for study of mitigation of hypoxic damage in the nervous system.