Targeted expression of tetanus toxin: a new tool to study the neurobiology of behavior

Over the past few decades, the explosion of molecular genetic knowledge, particularly in the fruit fly Drosophila melanogaster, has led to the identification of a large number of genes, which, when mutated, directly or indirectly affect fly behavior. Beyond the genetic and molecular characterization of genes and their associated molecular pathways, recent advances in molecular genetics also have allowed the development of new tools dedicated more directly to the dissection of the neural bases for various behaviors. In particular, the conjunction of the development of two techniques--the enhancer-trap detection system and the targeted gene expression system, based on the yeast GAL4 transcription factor--has led to the development of the binary enhancer-trap P[GAL4] expression system, which allows the selective activation of any cloned gene in a wide variety of tissue- and cell-specific patterns. Thus, this development, in addition to allowing the anatomical characterization of neuronal circuitry, also allows, via the expression of tetanus toxin light chain (known to specifically block synaptic transmission), an investigation of the role of specific neurons in certain behaviors. Using this system of "toxigenetics," several forms of behavior--from those mediated by sensory systems, such as olfaction, mechanoreception, and vision, to those mediated by higher brain function, such as learning, memory and locomotion--have been studied. These studies aim to map neuronal circuitry underlying specific behaviors and thereby unravel relevant neurophysiological mechanisms. The advantage of this approach is that it is noninvasive and permits the investigation of behavior in the free moving animal. We review a number of behavioral studies that have successfully employed this toxigenetic approach, and we hope to persuade the reader that transgenic tetanus toxin light chain is a useful and appropriate tool for the armory of neuroethologists.