Olfactory navigation in Drosophila as a model for multi-sensory integration

果蝇的嗅觉导航作为多感官整合的模型

• 批准号: 8874199
• 负责人: Katherine Nagel
• 金额: $ 24.65万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-16 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8874199
• 关键词: Accounting; Address; Algorithms; Animal Model; Animals; Area; Auditory; Behavior; Behavioral; Behavioral Paradigm; Biological Models; Biophysical Process; Brain; Brain region; Cells; Complex; Conflict (Psychology); Cues; Culicidae; Dependence; Drosophila genus; Environmental Wind; Food; Fruit; Genetic; Genetic Models; Genetic Techniques; Goals; Human; Insecta; Lateral; Learning; Lesion; Light; Link; Lobe; Location; Locomotion; Malaria; Methodology; Modality; Modeling; Motion; Motor; Mutation; Nervous system structure; Neurons; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Organism; Performance; Physiologic pulse; Play; Population; Postdoctoral Fellow; Probability; Property; Recruitment Activity; Research; Research Personnel; Role; Sensory; Shapes; Signal Transduction; Smell Perception; Songbirds; Sorting - Cell Movement; Source; Speed; Stimulus; Techniques; Testing; Training; Vision; Walking; Work; base; environmental change; fly; insight; neural circuit; neuromechanism; novel; programs; relating to nervous system; research study; response; sensory input; sensory integration; sensory stimulus; sensory system; synaptic depression; tool; way finding

DESCRIPTION (provided by applicant): Odors dispersed by the wind form turbulent plumes that contain only stochastic information about source location. A fly navigating towards an attractive odor must therefore combine olfactory cues with information about wind direction and self-motion to correctly locate its source. I propose to use olfactory navigation in the fruit-fly Drosophila as a model system for studying general questions about how neurons represent noisy real-world stimuli, how animals adapt their behavior to changing environmental conditions, and how neural circuits integrate information from multiple senses to guide behavior. My hope is that the genetic tools available in Drosophila will ultimately allow us to answer these questions at a mechanistic biophysical level. In the first part of my post-doc I examined how dynamic stimuli, including plumes, are encoded by olfactory receptor neurons (ORNs) in the Drosophila olfactory periphery (Nagel and Wilson, 2011). Previous studies had observed that ORNs show odor- and cell-dependent dynamics that would seem to make them poorly suited for encoding the rapid fluctuations seen in natural plumes. I found that I could explain these dynamics in terms of two biophysical processes, odor transduction and spiking. Odor transduction gives rise to the odor- and cell-dependence of ORN dynamics, while spiking increases both the complexity of responses, and their speed. This work drew on my graduate training quantifying the response properties of auditory neurons in the songbird (Nagel and Doupe, 2006, 2008). However, it also relied on genetic techniques that I learned during my post-doc. For the second part of my post-doc, I propose to extend this type of analysis to second order olfactory neurons. Specifically I propose to ask how second order neurons encode dynamic plume stimuli, and what circuit and synaptic mechanisms contribute to their responses. This project forms Aim #1 of this proposal. In working on this project I will learn new techniques, such as intracellular recording from central fly neurons. I will also learn to manipulate different parts of a neural circuit and to analyze the results of these experiments critically. Together with the first part of my post-doc, this study will form a template for how to link neural representations of sensory stimuli to biophysical mechanisms. As an independent investigator, I plan to expand my focus to look at the algorithms flies use to localize odor sources (Aim #2) and the central circuits involved in this behavior (Aim #3). This will allow me to differentiate my research program from that of my post-doctoral advisor, Rachel Wilson, and to begin to address larger questions about multi-sensory integration and behavioral choice. In Specific Aim #2, I propose three novel methodologies for studying olfactory navigation behavior. These approaches will allow me to quantify how flies integrate cues from multiple modalities to decide when to turn, stop, and advance. In Specific Aim #3, I propose to study how a candidate brain area, the central complex, contributes to these behaviors. Using intracellular recordings, I will ask whether neurons in this area carry the sort of spatial or directional information necessary for navigation. Using genetic lesions I will ask whether mutations of this area disrupt sensory integration or behavioral choice in predictable ways. Together these experiments will allow me to identify the main computations that the fly nervous system must perform in order to successfully localize an attractive odor and to test whether a particular brain area is likely to play an important role in these computations. Most importantly, these experiments will provide a basis for asking mechanistic questions about how sensory input is integrated to guide on-going behavior. Answering these questions is my long-term research goal.

描述（由申请人提供）：由风形湍流羽流分散的气味，这些羽毛仅包含有关源位置的随机信息。因此，朝着有吸引力的气味导航的苍蝇必须将嗅觉线索与有关风向和自我运动的信息相结合，以正确定位其来源。我建议将果蝇果蝇中的嗅觉导航作为一个模型系统，用于研究有关神经元如何代表嘈杂的现实世界刺激，动物如何使其行为适应改变环境条件的一般问题，以及神经回路如何从多种感觉中整合信息来指导行为。我的希望是，果蝇中可用的遗传工具最终将使我们能够在机械生物物理水平上回答这些问题。在我的大多数后的第一部分中，我检查了果蝇嗅觉外围的嗅觉受体神经元（ORN）如何编码动态刺激（包括羽流）（Nagel and Wilson，2011年）。先前的研究观察到，ORN显示出气味和细胞依赖性动力学，这似乎使它们不适合编码自然羽流中的快速波动。我发现我可以用两个生物物理过程，气味转导和尖峰来解释这些动态。气味转导引起ORN动力学的气味和细胞依赖性，而尖峰会增加响应的复杂性及其速度。这项工作吸引了我的研究生培训，以量化鸣禽中听觉神经元的反应特性（Nagel and Doupe，2006，2008）。但是，它也依赖于我在DOC期间学到的遗传技术。在我的大约第二部分的第二部分中，我建议将这种类型的分析扩展到二阶嗅觉神经元。具体而言，我建议询问二阶神经元如何编码动态羽状刺激，以及哪些电路和突触机制有助于其反应。该项目的目标是本提案的目标＃1。在从事该项目的过程中，我将学习新技术，例如中枢神经元的细胞内录制。我还将学会操纵神经回路的不同部分，并严格分析这些实验的结果。这项研究将与我的大多数人的第一部分一起，形成一个模板，用于如何将感觉刺激的神经表示与生物物理机制联系起来。 作为一名独立的研究者，我计划扩大重点，以查看用于本地气味来源（AIM＃2）和涉及此行为的中央电路的算法（AIM＃3）。这将使我能够将我的研究计划与博学后顾问瑞秋·威尔逊（Rachel Wilson）区分开来，并开始解决有关多感官集成和行为选择的更大问题。在特定的目标＃2中，我提出了三种研究嗅觉导航行为的新方法。这些方法将使我能够量化苍蝇如何整合来自多种模式的线索，以决定何时转弯，停止和进步。在特定的目标＃3中，我建议研究候选大脑区域（中心综合体）如何促进这些行为。使用细胞内记录，我将询问该区域的神经元是否携带导航所需的空间或方向信息。使用遗传病变，我将询问该区域的突变是否以可预测的方式破坏感觉整合或行为选择。这些实验将使我能够确定蝇神经系统必须执行的主要计算，以便成功地定位有吸引力的气味并测试特定的大脑区域是否可能在这些计算中起重要作用。最重要的是，这些实验将为询问有关如何集成感官输入以指导持续行为的机理问题的基础。回答这些问题是我的长期研究目标。