Neurobiology of peptidergic and aminergic neurons in insects.

昆虫肽能和胺能神经元的神经生物学。

• 批准号: RGPIN-2017-06402
• 负责人: Orchard, Ian
• 金额: $ 5.03万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691462
• 关键词: Neurobiology; peptidergic; aminergic; neurons; insects.

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.

我的研究项目的中心主题是神经系统的功能，用昆虫作为实验模型。我们正在建立神经系统传递信息的机制；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。我们所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？什么类型的化学物质作为这些信息的传递者，这些化学信息是如何被目标细胞翻译的？如何调节和协调这些信息，使动物产生适当的行为？特别是，我们对多肽和胺作为神经激素的作用感兴趣，释放到血液中以协调不同组织群的活动，并作为神经调节剂，调节不同途径的持续活动。******在过去的几年里，我们的工作主要集中在医学上重要的虫子，Rhodnius prolixus。这种虫子从人类身上摄取大量的血液，在随后排泄过量的盐和水（利尿）的过程中，这种寄生虫克氏锥虫被传播给人类宿主，并在那里引起恰加斯病。我们正在研究在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精确输入，导致血淋巴血清素和利尿肽激素的升高（由我们确定），描述释放这些利尿和抗利尿激素的神经分泌细胞的位置和生理特性，以及它们的靶部位（如唾液腺、中肠、后肠、马尔比氏小管、心脏和表皮细胞）。吸血也是生长、发育和繁殖的刺激因素，所以我们也在研究这些长期事件，以及类似神经肽家族的参与。******由于罗德尼斯基因组计划，这一领域的进展得到了促进和加强，我们首次在罗德尼斯成功地克隆了神经肽和gpcr基因，合成了神经肽并检查了它们的生理作用。******这项研究也为害虫防治策略奠定了基础，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，人们可以认为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。我们发现的利尿激素和可能更相关的抗利尿激素，是相当重要的。