I propose a disruptive technology that will revolutionize our understanding of brain function, development, and disease. Because the study of neural circuits remains deeply limited by a paucity of data, we need massively parallel approaches to brain imaging that will raise data acquisition rates by over two orders of magnitude. High-throughput technologies have already revolutionized certain areas of biology such as genomics and proteomics, but neuroscience has yet to experience a growth spurt of comparable magnitude. I will construct instrumentation allowing the brain volumes of ~100 alert flies to be imaged simultaneously by two-photon fluorescence microscopy. I have chosen the fruit fly, Drosophila melanogaster, because of its small brain, its sophisticated behavioral repertoire, the large number of strains with genetically targeted alterations to brain circuitry, the utility of fluorescence imaging of neural activity in this species, and the importance of the fly as a model for the study of many brain diseases. Massively parallel brain imaging will open entirely new avenues: 1) The ability to track neural dynamics across the brains of large numbers of normal flies and those with genetically induced neural circuit perturbations will revolutionize our understanding of how neural circuits produce animal behavior;2) The now prominent role of the fruit fly as a model system for the study of developmental disorders, neurodegenerative diseases, and addiction implies we will gain significant medical insights into devastating conditions;3) Our technology will have important applications to drug screening, allowing the cellular effects of new compounds to be assessed rapidly in vivo;4) The ability to perform high-throughput time-lapse imaging of cellular events during the maturation of fly embryos will allow an additional revolution in developmental neurobiology. Applications of our technology will also be plentiful in other model organisms such as nematodes and zebrafish, profoundly impacting multiple areas of biomedicine.
