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）：气味被风分散形成湍流羽流，其中只包含有关源位置的随机信息。因此，苍蝇朝着吸引人的气味飞行时，必须将嗅觉线索与风向和自我运动信息结合起来，才能正确定位气味的来源。我建议使用果蝇的嗅觉导航作为模型系统来研究神经元如何代表嘈杂的现实世界刺激，动物如何适应不断变化的环境条件，以及神经回路如何整合来自多种感官的信息来指导行为。我希望在果蝇身上可用的遗传工具最终能让我们在机械生物物理层面上回答这些问题。在我博士后的第一部分，我研究了动态刺激，包括羽毛，是如何被果蝇嗅觉外围的嗅觉受体神经元（orn）编码的（Nagel和Wilson， 2011）。先前的研究已经观察到，orn表现出气味和细胞依赖的动态，这似乎使它们不太适合编码自然羽流中出现的快速波动。我发现我可以用两种生物物理过程来解释这些动态，气味转导和刺突。气味转导引起了ORN动力学对气味和细胞的依赖性，而尖峰反应增加了反应的复杂性和速度。这项工作借鉴了我的研究生训练，量化了鸣禽听觉神经元的反应特性（Nagel和Doupe， 2006年，2008年）。然而，它也依赖于我在博士后期间学到的基因技术。在我博士后的第二部分，我建议将这种分析扩展到二级嗅觉神经元。具体来说，我建议询问二阶神经元如何编码动态羽流刺激，以及哪些电路和突触机制有助于它们的反应。这个项目构成了本提案的第一个目标。在这个项目中，我将学习新的技术，比如中央果蝇神经元的细胞内记录。我还将学习如何操作神经回路的不同部分，并批判性地分析这些实验的结果。与我博士后的第一部分一起，这项研究将形成一个如何将感觉刺激的神经表征与生物物理机制联系起来的模板。作为一名独立调查员，我计划扩大我的研究重点，看看苍蝇用来定位气味来源的算法（目标#2）和参与这种行为的中央电路（目标#3）。这将使我的研究项目与我的博士后导师Rachel Wilson的研究项目有所区别，并开始解决有关多感觉整合和行为选择的更大问题。在Specific Aim #2中，我提出了三种研究嗅觉导航行为的新方法。这些方法将允许我量化苍蝇如何整合来自多种模式的线索来决定何时转弯、停止和前进。在具体目标#3中，我建议研究一个候选的大脑区域，即中央复合体，是如何影响这些行为的。通过细胞内记录，我将询问这个区域的神经元是否携带导航所必需的空间或方向信息。利用基因损伤，我将询问该区域的突变是否会以可预测的方式破坏感觉整合或行为选择。总之，这些实验将使我能够确定苍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发挥重要作用。最重要的是，这些实验将为提出关于如何整合感官输入来指导正在进行的行为的机制问题提供基础。回答这些问题是我长期研究的目标。