Growth Proteins and Synaptic Plasticity

Northwestern University, Evanston IL

Investigators

Abstract

Abstract for Lay Audience -Routtenberg Perhaps the most unnerving experiences in our intellectual lives is the frustration of forgetting. It is the over-arching view of the proposed research that 'why we forget' has to do with the faulty chemistry of the brain connections that form the memory network. Indeed we have recently discovered using a model system of brain memory that we can prevent memory storage and its retrieval. Then, by giving a drug that activates a signalling pathway that our laboratory described, we can reactivate the memory. Put another way, the key that turns on memory and its retrieval may be like that used in the car's ignition. What we have done is moved to the next stage and 'hot-wired' memory processes, by-passing the initial switch. This pathway is thus critical to memory formation and retrieval. Our studies employ gene targeting methods in transgenic mice to modify the switches and signalling mechanisms (gene products or proteins, one and all) that regulate both the chemistry of the brain connections and as a consequence the memory storage process. We study the most widely used physiological model of memory, long-term potentiation, which monitors the events that occur at the synapse at the time when model memories are being stored. We complement the gene targeting with pharmacological tools that allow us to confirm with converging lines of evidence the identified sequence of events involved in the storage of information. Since gene manipulation is not feasible in humans, this complimentary approach provides the basis for drug discovery in the context of current molecular biological technologies and suggest novel strategies in the war against cognitive and memory disorders.