The Circuit Logic of Modulation of Locomotion by Odors

气味调节运动的电路逻辑

• 批准号: 10026312
• 负责人: Vikas Bhandawat
• 金额: $ 24.29万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10026312
• 关键词: Circuit; Logic; Modulation; Locomotion; Odors

1 There is a fundamental gap in our understanding of the circuit mechanisms underlying even simple naturalistic 2 behaviors, such as making a cup of coffee, which proceed through a sequential execution of sub-behaviors. 3 Continued existence of this gap represents an important problem because obtaining a circuit-level understand- 4 ing of complex multi-step behaviors is a necessary step toward unlocking the mysteries of healthy brain func- 5 tion and of disorders. The overarching goal is to obtain a circuit-level understanding of such naturalistic behav- 6 ior. The research objective here is to unravel the logic of sensorimotor transformation in the context of odor- 7 modulation of locomotion in Drosophila. The central hypothesis is that, like many of our own everyday actions, 8 control of odor-modulation of locomotion is hierarchical. A fly’s locomotion is built from simpler elements called 9 locomotor primitives, each of which lasts between 1-3 seconds (or 10-30 steps). Odors, instead of acting on 10 instantaneous locomotor parameters such as speed and angular speed, act on these locomotor primitives and 11 change the probability that the fly spends performing a given locomotor primitive. This hypothesis was formu- 12 lated on the basis of our previous work and preliminary data. The rationale for the proposed research is that 13 understanding odor-guided locomotion—a complex, flexible behavior—in the context of a genetically tractable 14 system will allow a precise delineation of the steps that underlie sensorimotor transformation in the context of a 15 naturalistic behavior. The hypothesis above will be tested by characterizing the circuit basis of modulation of 16 locomotion by food odors using a combination of techniques including imaging, electrophysiology, quantitative 17 behavior and computation. The proposed research has three specific aims. 1) To extract the locomotor primi- 18 tives and test the hypothesis that odors modulate locomotion by changing the time a fly spends performing dif- 19 ferent locomotor primitives. 2) To test the hypothesis that different ORN classes modulate the time spent in 20 distinct locomotor primitives. 3) To elucidate the role of lateral horn in odor modulation of locomotion. The re- 21 search is innovative because it employs sophisticated statistical tool (Hierarchical Hidden Markov model, 22 HHMM) and cutting-edge experimental tools in the context of a genetically tractable model organism to obtain 23 insights into naturalistic behaviors. The proposed research is significant because it will vertical advance our 24 understanding of sensorimotor processes involved in naturalistic behaviors. Insights from multiple fields have 25 all come to the conclusion that behavior is organized into discrete packets or behavioral primitives. Actions un- 26 fold by a sequential recruitment of these discrete packets. A critical barrier to the study of natural behavior is 27 that in most cases there is enough variability in these discrete packets to make them unrecognizable without 28 the help of sophisticated statistical tool. By deploying HHMM, we overcome this critical barrier. Besides repre- 29 senting a vertical advance in our understanding of naturalistic behavior, another possible positive outcome of 30 this study is better diagnosis of neurological conditioning that occur through improper sequencing of actions. 31 32 33

1 即使是简单的自然主义，我们对电路机制的理解也存在根本差距 2 个行为，例如泡一杯咖啡，通过顺序执行子行为来进行。 3 这种差距的持续存在代表着一个重要的问题，因为获得电路级的理解 4 复杂的多步骤行为是解开健康大脑功能之谜的必要步骤 5 重刑和疾病。总体目标是获得对这种自然行为的电路级理解 6 或。这里的研究目标是阐明气味背景下感觉运动转换的逻辑 7 果蝇运动的调节。中心假设是，就像我们自己的许多日常行为一样， 8 运动气味调节的控制是分层的。苍蝇的运动是由更简单的元素构成的，称为 9 个运动基元，每个持续 1-3 秒（或 10-30 步）。气味，而不是作用于 10 个瞬时运动参数，例如速度和角速度，作用于这些运动基元并 11 改变苍蝇执行给定运动原语的概率。这个假设是公式化的 12 根据我们之前的工作和初步数据得出的。拟议研究的理由是 13 在遗传易处理的背景下理解气味引导的运动——一种复杂、灵活的行为 14 系统将允许精确描述在感觉运动转换的背景下的步骤 15 自然行为。上述假设将通过表征调制的电路基础来检验 16 结合成像、电生理学、定量等技术，通过食物气味进行运动 17 行为和计算。拟议的研究有三个具体目标。 1）提取运动原 18 试验并检验气味通过改变果蝇执行不同动作的时间来调节运动的假设 19 个不同的运动原语。 2) 检验不同 ORN 类调节花费时间的假设 20 种不同的运动原语。 3）阐明侧角在运动气味调节中的作用。那里- 21 搜索之所以具有创新性，是因为它采用了复杂的统计工具（分层隐马尔可夫模型、 22 HHMM）和在遗传上易处理的模型生物背景下的尖端实验工具，以获得 23 对自然行为的见解。拟议的研究意义重大，因为它将垂直推进我们的研究 24 了解自然行为中涉及的感觉运动过程。来自多个领域的见解 25 人都得出这样的结论：行为被组织成离散的数据包或行为原语。行动非 通过连续招募这些离散数据包可实现 26 倍。研究自然行为的一个关键障碍是 27 在大多数情况下，这些离散数据包中有足够的可变性，使它们无法在没有 28 精密统计工具的帮助。通过部署 HHMM，我们克服了这一关键障碍。除了代表 29 使我们对自然行为的理解产生了纵向进步，这是另一个可能的积极成果 30 这项研究可以更好地诊断因不正确的动作顺序而发生的神经病症。 31 32 33