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2 Circuit-breaking and Behavioral Analysis by Molecular Genetic Manipulation of Neural Activity in Drosophila

Todd C. Holmes, Vasu Sheeba, Doğukan Mizrak, Bálint Rubovszky, David Dahdal


Many advances toward understanding neural circuits and the control of behavior have been achieved using invertebrate organisms (Marder 2002; Greenspan 2005). Although larger invertebrates are amenable to electrophysiological and behavioral investigation, many such organisms cannot be genetically manipulated or easily studied using forward genetics. Invertebrate neurobiology is enjoying a renaissance for integrative neural circuit analysis that spans molecular action to whole-animal behavior using the genetically tractable fruit fly Drosophila melanogaster. Systems neuroscience, behavioral analysis, molecular genetics, biophysics, and protein engineering have now converged to an exciting new set of tools for manipulating neural activity in behaving flies. Although these new tools have widely different molecular targets and mechanisms of action, they all share a common purpose for understanding neural circuits through effecting selective perturbation of neural activity: thus, we will refer to means of manipulating neural activity collectively as circuit-breaking effectors. One way to understand how something works is to break part of it and see what happens. Systems neuroscience has historically relied on the lesion approach. Emerging methods go beyond the lesion approach by inducing neural inactivation or increased neural activity in specific neurons, or altering synaptic transmission between neurons. Our growing ability to systematically alter and physiologically measure neural activity in Drosophila represents a tremendous advance for integrative neuroscience as a science of control and causality rather than a science of observation and correlation.

The first means for examining nerve and muscle excitability in Drosophila came through the study of ion channel mutants. Potassium...

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