ABSTRACT
Introduction............................................................................................................ 333 23.1 Visualizing Neuronal Circuits Thanks to Genetics ..................................... 338 23.2 Imaging Brain Activity ................................................................................ 339 23.3 Learning and Memory Mutants ................................................................... 340 23.4 Temporal Control of Gene Expression........................................................ 341 23.5 A Tool to Build Anatomo-Functional Maps ............................................... 343 23.6 Localization of Olfactory Memory in Drosophila MBs ............................. 343 23.7 Dynamic of Olfactory Memory Phases in Drosophila ............................... 345 References.............................................................................................................. 348
Drosophila melanogaster is one of the most intensively studied organisms in biology, and it serves as a model system for the investigation of many cellular, developmental and behavioral processes common to other species, including humans. This holds true in particular for brain studies, as Drosophila central nervous system is made of neurons and glia that operate on the same fundamental principles as their mammalian counterparts. Thus, most neurotransmitters are identical in flies and humans, and despite the fact that the Drosophila brain has only 100,000 cells,1 it produces complex behaviors and sustains various forms of learning and memory. Besides studies of fundamental brain properties, fly models are being developed for a variety of neurodegenerative disorders, and the field is beginning to harness the power of Drosophila genetics to dissect pathways of disease pathogenesis and identify potential targets for therapeutic intervention. This approach is possible because about 50% of human genes have a Drosophila ortholog.2 In addition, transgenic strategies that allow to introduce human genes into Drosophila continue to expand the list of modeled diseases, which now includes Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and several spinocerebellar ataxias.3,4
During the past few decades, the pool of molecular genetics techniques that apply to the fruit fly has increased enormously. It has been a long time since the selection of randomly and chemically produced mutants was the most common technique to analyze genes function. Nowadays, the extensive use of transposable element-induced mutations allows a much faster identification and study of genes involved in a given developmental or physiological pathway. Once combined with the systematic generation of high-resolution deletions, this global approach should eventually provide researchers with a complete mutant collection (see Table 23.1).5,6
Moreover, new techniques have arisen that permit one to directly disturb the expression of a defined gene, without the need of performing a mutagenesis. Rong7-9 and colleagues have developed the technique of homologous recombination in Drosophila. This technique, however, remains heavy. The development of the interference RNA (RNAi) combined with the P[GAL4] enhancer-trap system allows one to inhibit the expression of any gene of interest in almost any group of cells-for example, in a particular brain circuit.10
