A long-term goal of Dr. Truman's program is to understand the role of endocrine factors in the regulation of behavior. This work has focussed on an insect peptide hormone, the eclosion hormone (EH). Studies on moths 20 years ago first indicated the existence of this hormone, and it is now known to be found throughout the insects. Its sole known function is to trigger the behavioral and physiological changes that occur at ecydsis, the time at the end of each molt when the insect sheds to old skin of the former stage. The major target of EH is the central nervous system, which responds to the hormone with a stereotyped program of patterned motor activity which is the basis for the ecdysis behavior. The PI and his colleagues have focussed on two aspects of the ecydsis system: 1) the factors that control the release of EH and 2) the mode of action of this peptide on the nervous system. The system has proven to be very favorable in both regards. The studies in the present proposal are based on a number of advances over the past few years: the determination of the complete structure of EH and production of antibodies against it, the isolation and cloning of the gene that codes for this hormone, and the identification of the neurons that produce and secrete EH. The latter neurons, termed the ventrolateral (VM) cells have a unique position in the brain and send their axons the length of the ventral nervous system to a release site along the hindgut. They appear to be the only neurosecretory cells that project to this area. Their unique position as well as the levels of hormone that they release at each episode (about 90%) make them excellent cells in which to study ultrastructural features of hormone release and of restocking. Also, these cells are very accessible for electrophysiological studies and intracellular and extracellular recording techniques will be used to determine the electrical changes in these cells that result in EH secretion. During the molts of the immature stages, the decline in the levels of steroid hormones at the end of each molt is both necessary and sufficient to cause EH release but then EH, itself, appears to act back to shut-off its own secretion. In the adult, by contrast, these cells respond not only to steroid decline but also to the input from a circadian clock.
