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A brain protein called CREB is centrally involved in the formation of new memories. Drugs that enhance CREB have been shown to improve learning and memory in animals. In the words of Dr. Tully, CREB drugs create “photographic” memory capabilities. This new class of drugs might be particularly useful for “normal aging”, as well as Alzheimer’s disease. The advantage of CREB drugs is a significant reduction in the amount of time needed to commit new learning to long-term memory. Helicon Therapeutics, Inc., a small biotechnology company was founded in 1997 with a mission to discover and develop new drugs that improve memory by advancing the work of Dr. Tully. Working in collaboration with a pharmaceutical company called Hoffman LaRoche, Helicon has identified a number of new CREB compounds. In this proposal, Helicon will evaluate the 10 lead CREB compounds in a number of animal models of memory and, determine the precise mode of action of these novel drugs.