Genes and Neural Circuits Mediating Avoidance Behavior

描述（由申请人提供）：特定的感觉刺激如何引起特定的行为是神经生物学中的一个基本问题。大多数气味引起吸引或回避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神经元（OSN）的组合，使将气味识别转化为行为的回路的解剖复杂化。相比之下，二氧化碳（CO2），在苍蝇，黑腹果蝇，并激活只有两个群体的OSN的浓度范围很宽，在体内钙成像技术检查时，eleclamping避免。先前的研究表明，表达GR63a和GR21a受体的OSNs是第一个被发现的CO2嗅觉神经元，对于避免低浓度的CO2是必不可少的，但仍不清楚CO2激活的其他神经元的功能。在这里，我们建议确定，推定的第二CO2 OSNs和它的同源受体，属于最近确定的离子型谷氨酸受体（IR）家族的成员是必要的和足够的检测和避免高CO2浓度和类似的气味，如酸。为了解决这些问题，我们将进行体内钙成像和行为测定。确定第二CO2受体的亚细胞定位将预测受体是否直接与气味剂相互作用。为了更好地了解中央回路介导的回避行为，我们将跟踪其投射到更高的大脑中心，并将其与第一CO2通路进行比较，无论这两条通路是否会聚在更高的大脑中心（如侧角）的同一个目标神经元上。由于温血宿主释放的CO2和酸是蚊子的基本嗅觉线索，并且第二CO2受体的同源物在蚊子触角中表达，我们计划检查表达同源物的蚊子OSN是否被CO2和酸激活。 公共卫生相关性：昆虫将疾病传播给人类和包括牲畜在内的动物，并对健康造成严重威胁，对农业产量造成巨大损失。许多昆虫主要通过二氧化碳（CO2）和乳酸对人类和动物宿主做出反应，这是哺乳动物发出的关键嗅觉线索。这些嗅觉信号激活了蚊子中特定的嗅觉感觉神经元群，这些神经元表达与果蝇相同的气味受体。了解果蝇感觉受体如何被CO2和酸激活，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来预防蚊子，采采蝇和其他病原昆虫传播的昆虫传播疾病。

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.