Neurotrapping: cellular screens to identify the neural substrates of behavior in Drosophila

The availability of new tools for manipulating neuronal activity, coupled with the development of increasingly sophisticated techniques for targeting these tools to subsets of cells in living, behaving animals, is permitting neuroscientists to tease apart brain circuits by a method akin to classical mutagenesis. Just as mutagenesis can be used to introduce changes into an organism's DNA to identify the genes required for a given biological process, changes in activity can be introduced into the nervous system to identify the cells required for a given behavior. If the changes are introduced randomly, the cells can be identified without any prior knowledge of their properties. This strategy, which we refer to here as "neurotrapping," has been implemented most effectively in Drosophila, where transgenes capable of either suppressing or stimulating neuronal activity can be reproducibly targeted to arbitrary subsets of neurons using so-called "enhancer-trap" techniques. By screening large numbers of enhancer-trap lines, experimenters have been able to identify groups of neurons which, when suppressed (or, in some cases, activated), alter a specific behavior. Parsing these groups of neurons to identify the minimal subset required for generating a behavior has proved difficult, but emerging tools that permit refined transgene targeting are increasing the resolution of the screening techniques. Some of the most recent neurotrapping screens have identified physiological substrates of behavior at the single neuron level.