Neurogenetic approaches to habituation and dishabituation in Drosophila

We review work in the major model systems for habituation in Drosophila melanogaster, encompassing several sensory modalities and behavioral contexts: visual (giant fiber escape response, landing response); chemical (proboscis extension reflex, olfactory jump response, locomotory startle response, odor-induced leg response, experience-dependent courtship modification); electric (shock avoidance); and mechanical (leg resistance reflex, cleaning reflex). Each model system shows several of Thompson and Spencer's [Thompson, R. F., & Spencer, W. A. (1966). Habituation: A model phenomenon for the study of neuronal substrates of behavior. Psychological Review, 73, 16-43] parametric criteria for habituation: spontaneous recovery and dishabituation have been described in almost all of them and dependence of habituation upon stimulus frequency and stimulus intensity in the majority. Stimulus generalization (and conversely, the delineation of stimulus specificity) has given insights into the localization of habituation or the neural architecture underlying sensory processing. The strength of Drosophila for studying habituation is the range of genetic approaches available. Mutations have been used to modify specific neuroanatomical structures, ion channels, elements of synaptic transmission, and second-messenger pathways. rutabaga and dunce, genes of the cAMP signal pathway that have been studied most often in the reviewed experiments, have also been implicated in synaptic plasticity and associative conditioning in Drosophila and other species including mammals. The use of the Gal4/UAS system for targeting gene expression has enabled genetic perturbation of defined sets of neurons. One clear lesson is that a gene may affect habituation differently in different behaviors, depending on the expression, processing, and localization of the gene product in specific circuits. Mutations of specific genes not only provide links between physiology and behavior in the same circuit, but also reveal common mechanisms in different paradigms of behavioral plasticity. The rich repertoire of models for habituation in the fly is an asset for combining a genetic approach with behavioral, anatomical and physiological methods with the promise of a more complete understanding.