Neurobiology of peptidergic and aminergic neurons in insects.

点击翻译按钮获取中文摘要

The central theme of my research program is the functioning of the nervous system, using insects as experimental models. We are establishing the mechanisms by which the nervous system communicates information; examining hormonal, synaptic, and modulatory mechanisms, using neurophysiological, neurochemical, endocrinological, and molecular biological techniques. The questions we are asking are fundamentally important for all nervous systems: How can a neuron transmit information to a target cell? What types of chemicals act as the transmitters for this information and how are these chemical messages translated by the target cell? How can this information be modulated and coordinated to produce an appropriate behaviour in the animal? In particular, we are interested in the role of peptides and amines as neurohormones, released into the blood to co-ordinate activities of diverse groups of tissues, and as neuromodulators, modulating the ongoing activities of distinct pathways. Our work over the past few years has focused particularly on the medically-important bug, Rhodnius prolixus. This bug takes enormous blood meals from humans, and during the subsequent excretion of excess salts and water (diuresis), the parasite, Trypanosoma cruzi, is transmitted to the human host where it causes Chagas disease. We are examining a variety of short-term events which occur following the natural stimulus of a blood meal, including the neurohormonal control of diuresis, and also the cessation of diuresis. In particular, we are defining the precise input associated with feeding which results in elevations in haemolymph serotonin and diuretic peptide hormones (identified by us), describing the location and physiological properties of the neurosecretory cells which release these diuretic and anti-diuretic hormones, and their target sites (e.g. salivary glands, midgut, hindgut, Malpighian tubules, heart and epidermal cells). Blood-gorging is also the stimulus for growth, development and reproduction, and so we are also studying these longer term events, and the involvement of similar families of neuropeptides. Progress in this area has been facilitated and enhanced because of the Rhodnius genome project, and we have been successful in cloning, for the first time in Rhodnius, the genes for neuropeptides and GPCRs, synthesising the neuropeptides and examining their physiological effects. This research also lays the foundation for pest control strategies, targeting neuropeptides as lead compounds. Since the parasite is transmitted during diuresis, one can argue that diuretic hormones actually control the transmission of Chagas disease. Interfering with this process should interfere with the transmission of Chagas disease. Our discovery of the diuretic and possibly more relevant antidiuretic hormones, is of some considerable importance.