Abstract
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.
Highlights
The fields of neuroscience and genetics face similar challenges: Both must explain how elementary components – neurons in the first case and genes in the second – interact to govern complex processes, such as behavior or development
Geneticists, lacking any knowledge of the basic unit of inheritance, were forced to take a different approach: They started at the top, working from the organismal phenotypes that resulted from unknown changes in the genetic material, and made their way down to the gene
Neuroscience research has lacked a counterpart to the unbiased screen of genetics: While electrophysiological, pharmacological, anatomical, and genetic manipulations have each provided productive avenues to perturbing brain function, there has been no general method for systematically and randomly altering neuronal activity in freely behaving animals to identify the neurons underlying a given behavior. Such a method would usefully complement classic circuit-mapping techniques by supplying causal links to circuit maps derived from tracing synaptic connections and correlating activities
Summary
Neurotrapping: cellular screens to identify the neural substrates of behavior in Drosophila. Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD, USA. University of California, USA Ines Ibañez-Tallon, Max Delbrück Center for Molecular Medicine, Germany. 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
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