Neurobiology of peptidergic and aminergic neurons in insects.

我的研究计划的中心主题是神经系统的功能，使用昆虫作为实验模型。我们正在建立神经系统交流信息的机制；使用神经生理学、神经化学、内分泌学和分子生物学技术，检查激素、突触和调节机制。我们正在问的问题对所有神经系统来说都是至关重要的：神经元如何将信息传递给目标细胞？哪些类型的化学物质充当这种信息的传递者，这些化学信息是如何被目标细胞翻译的？这种信息如何被调节和协调，以在动物身上产生适当的行为？特别是，我们对多肽和胺作为神经激素的作用感兴趣，这些激素被释放到血液中协调不同组织的活动，以及作为神经调节器，调节不同途径正在进行的活动。*我们过去几年的工作特别集中在具有重要医学意义的Rhodnius prolixus上。这种细菌从人类身上摄取大量的血液，在随后排出过量的盐分和水(利尿)的过程中，寄生虫克氏锥虫被传播到人类宿主，在那里它会导致恰加斯病。我们正在研究血餐自然刺激后发生的各种短期事件，包括利尿的神经激素控制，以及利尿的停止。特别是，我们正在定义与喂养相关的导致血淋巴5-羟色胺和利尿性多肽激素水平升高的精确输入(由我们确定)，描述释放这些利尿剂和抗利尿剂激素的神经分泌细胞的位置和生理特性，以及它们的目标部位(例如唾液腺、中肠、后肠、马氏管、心脏和表皮细胞)。吞噬血液也是生长、发育和繁殖的刺激，所以我们也在研究这些较长期的事件，以及类似的神经肽家族的参与。*由于罗德纽斯基因组计划，这一领域的进展得到了促进和加强，我们首次在罗德纽斯成功地克隆了神经肽和GPCRs的基因，合成了神经肽并检测了它们的生理效应。*这项研究也为害虫控制策略奠定了基础，以神经肽为先导化合物。由于寄生虫是在利尿过程中传播的，人们可以争辩说，利尿激素实际上控制了恰加斯病的传播。干扰这一过程应该会干扰恰加斯病的传播。我们对利尿剂和可能更相关的抗利尿激素的发现，具有相当重要的意义。

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.