Our long-term goal is to understand how animals remember past experiences. The behavioral properties and cellular mechanisms of memory are highly similar across animal phyla. This means that many features of memory can be studied in simple organisms that are easy to manipulate (Fly Learning Movie). The immensely powerful genetic techniques that are feasible in fruit flies make for an ideal "model system" to study this problem. Work in the lab consists of four experimental approaches. The first is to use DNA microarrays to identify genetic pathways that are involved in Pavlovian learning and memory. With this strategy, we have identified a number of genes involved in the sub-cellular transport of mRNAs and the local control of their translation (Dubnau et al., 2003). We hypothesize that these genes are involved in selectively modifying specific synaptic connections in response to environmental experience. Ongoing work is designed to investigate this hypothesis in mechanistic detail, in part by searching for the relevant translational targets of pumilio-dependent regulation.

A second area of focus in the lab is a genetic investigation of the anatomical pathways underlying each of the phases of memory. We are using a genetic technique to map the circuitry involved in memory processing in flies. Using a genetically engineered variant of dynamin protein, we can transiently shut down specific groups of neurons in living animals. With this approach we can quickly take sub-regions of the brain "offline" and then moments later bring them "online" again. This technique allows us to dissect the complex circuitry that is involved in learning, in memory storage, and even in memory recall (Dubnau et al., 2001). We are using this approach to dissect the anatomical circuitry underlying memory formation in this model system (Functional Anatomy Project).