David L. Deitcher - US grants

The nervous system of all animals is composed of cells called neurons. These neurons communicate with each other by releasing (secreting) packets of chemicals called neurotransmitters and neuropeptides which signal other neurons. This interneuronal communication is the way the nervous system processes information, and modulation of this process underlies learning and memory. The release of neurotransmitters and neuropeptides is thought to be controlled by a set of proteins called the SNAREs. Just how these SNARE proteins function has remained elusive despite intensive study. The SNARE proteins are highly conserved in all animals and similar proteins have even been identified in yeast. Thus, by studying SNARE function in the fruit fly Drosophila melanogaster, the function of the SNARE proteins can be applied to the secretory process in all animals. With the use of selected SNARE mutants, transgenic expression of SNARE genes in Drosophila, and a novel neuropeptide release assay, the function of these proteins in neurotransmitter and neuropeptide release will be determined.

Elucidating the process of neurotransmitter and neuropeptide release is essential for understanding behavior. More complex functions in the nervous system such as learning and memory involve alterations in synaptic strength. One major way of altering synaptic strength is by modulating the process of neurotransmitter release. Without a clear understanding of the fundamental mechanism of neurotransmitter release (the goal of this proposal), there is little chance of truly understanding the fascinating nature of learning and memory. Neuropeptides have other crucial functions in maintaining organismal homeostasis. Water balance, reproductive behavior, thirst, hunger, metabolic regulation, stress, sleep, and circadian rhythms are all controlled by neuropeptide release.

Neuropeptide secretions from the nervous and endocrine systems are used to precisely coordinate organ systems within the animal so that they function together, leading to a state of balance. Thus, determining how neuropeptide release is governed will greatly improve our understanding of how all animals regulate these complex organ systems. In light of evidence that environmental pollutants are capable of disrupting endocrine function by mimicking hormones, the studies in this proposal are crucial for defining normal endocrine function. These studies will also contribute to the defining the basic process of secretion on which all eukaryotic cells need for survival. The results of this work will be published in widely read journals for scientists and the scientific materials produced will be readily available to the scientific community. In fact, one such strain has already been donated to the Bloomington Drosophila Stock Center, making it readily available to all researchers. Furthermore, at Cornell University, two courses will include material from these studies to extend the educational goals of this research. Cornell's diverse student body ensures that scientific training will extend to underrepresented minorities in the sciences.