Associative conditioning between odor and pain in larval Drosophila

The study of olfactory learning and memory in adult Drosophila has been enormously productive, leading to the discovery of many conserved molecules and circuit motifs that mediate the formation and recall of associative odor memories. However, a level of understanding that attains complete cellular resolution requires that all relevant sensory inputs, i.e., both conditioned and unconditioned stimuli, are precisely mapped from the sensory periphery to the brain to the motor circuits that implement behavior. We propose to develop such a model using the Drosophila larva. Owing to the simplicity of larva movement, it has recently become possible to fully decompose its strategies for locomotory behavior and navigational decision-making in terms of stimulus-evoked modulations of a small number of motor programs. This provides a rigorous starting point for mechanistic understanding of innate and learned algorithms for navigating a stimulus environment. Another key advantage of the larva is that its nervous system is numerically simple and that excellent genetic tools exist to selectively target individual neuron classes. This offers a unique opportunity to identify key cellular and molecular players involved in forming, storing and recalling memories.