Genes and Neural Circuits Mediating Avoidance Behavior

描述(申请人提供)：特定的感官刺激如何引起特定的行为是神经生物学的一个基本问题。大多数气味会引起吸引或回避，这取决于它们的浓度和身份，以及它们激活的神经回路的性质。此外，这种气味通常会激活嗅觉感觉神经元(OSN)的组合，使将气味识别转化为行为的电路解剖变得复杂。相比之下，二氧化碳(CO2)在果蝇体内引起了对大范围浓度的回避，当用灵敏的体内钙成像技术检查时，只激活了两个OSNs种群。以前的研究表明，表达GR63a和GR21a受体的OSNs是最早被发现的CO2嗅觉神经元，对于避免低浓度CO2是必不可少的，但尚不清楚CO2激活的其他神经元的功能。在这里，我们建议确定推测的第二个CO2 OSNs及其同源受体属于最近发现的离子型谷氨酸受体(IRS)家族的一个成员，对于检测和避免高CO2浓度和类似的气味(如酸)是必要的和充分的。为了解决这些问题，我们将进行体内钙成像和行为分析。确定第二个二氧化碳受体的亚细胞定位将预测该受体是否直接与气味相互作用。为了更好地了解调节回避行为的中枢回路，我们将追踪其向高级大脑中心的投射，并将其与第一条二氧化碳通路进行比较，以确定这两条通路是否会聚在高等大脑中枢(如侧角)的同一靶神经元上。由于温血宿主释放的二氧化碳和酸是蚊子必不可少的嗅觉线索，而且第二个二氧化碳受体的同源物在蚊子的触角中表达，我们计划检测表达同源物的蚊子OSN是否被二氧化碳和酸激活。 公共卫生相关性：相关昆虫将疾病传播给人类和动物，包括牲畜，并对健康造成严重威胁，并对农业产量造成巨大损失。许多昆虫对人类和动物宿主的反应主要是通过二氧化碳(CO2)和乳酸，这是哺乳动物发出的关键嗅觉线索。这些嗅觉线索激活了蚊子中特定群体的嗅觉感觉神经元，这些神经元表达与果蝇相同的气味感受器。了解果蝇的感觉受体是如何被二氧化碳和酸激活的，以及它们的神经回路触发对这些刺激的行为反应的机制，将有助于我们制定更好的策略，以防止蚊子、采采蝇和其他病原体昆虫传播昆虫传播疾病。

DESCRIPTION (provided by applicant): How specific sensory stimuli evoke specific behaviors is a fundamental problem in neurobiology. Most odorants elicit attraction or avoidance depending on their concentrations and identity, as well as the nature of the neural circuits they activate. Such odorants, moreover, typically activate combinations of olfactory sensory neurons (OSNs), complicating the dissection of the circuits translating odor recognition into behavior. Carbon dioxide (CO2), in contrast, elicits avoidance over a wide range of concentrations in the fly, Drosophila melanogaster, and activates only two populations of OSNs when examined by a sensitive, in vivo calcium imaging technique. Previous studies showed that OSNs expressing GR63a & GR21a receptors, the first CO2 olfactory neurons identified, is essential for avoidance to low concentrations of CO2, but it remained unclear the function of the other neurons activated by CO2. Here, we propose to determine that the putative 2nd CO2 OSNs and its cognate receptor that belongs to a member of the recently identified Ionotropic Glutamate Receptors (IRs) family are necessary and sufficient for detection of and avoidance to high CO2 concentrations and similar odorants such as acids. To address these questions, we will perform in vivo calcium imaging and behavioral assays. Determining subcellular localization of the 2nd CO2 receptor will predict whether or not the receptor directly interacts with odorants. To better understand central circuits mediating avoidance behavior, we will trace its projections into higher brain centers and compare them to the 1st CO2 pathway whether these two pathways converge upon a same target neuron in a higher brain center such as the lateral horn. Because CO2 and acids released by warm-blooded hosts are essential olfactory cues for the mosquito, and a homolog of the 2nd CO2 receptor is expressed in the mosquito antenna, we plan to examine whether the mosquito OSNs expressing the homolog are activated by CO2 and acids. PUBLIC HEALTH RELEVANCE: Relevance Insects transmit diseases to humans and animals including livestock, and cause serious threats to health and enormous losses to agricultural output. Many insects respond to their human and animal hosts primarily through carbon dioxide (CO2) and lactic acid, key olfactory cues emanating from mammals. These olfactory cues activate defined populations of olfactory sensory neurons in the mosquito that express the same odorant receptors as in Drosophila. Understanding how the Drosophila sensory receptors are activated by CO2 and acids, and the mechanism by which their neural circuits trigger behavioral responses to these stimuli would help us develop better strategies to prevent transmission of insect-born diseases by mosquitoes, tsetse flies, and other pathogenic insects.