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The Circuit Logic of Modulation of Locomotion by Odors

气味调节运动的电路逻辑

基本信息

批准号：
10132287
负责人：
Vikas Bhandawat
金额：
$ 32.52万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

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我们对电路机制的理解存在根本性的差距，即使是简单的自然主义。 2个行为，例如冲一杯咖啡，其通过子行为的顺序执行来进行。 3这种差距的持续存在是一个重要的问题，因为获得电路级的理解- 研究复杂的多步行为是揭开健康大脑功能奥秘的必要一步。五是失序和无序。首要目标是获得电路级的理解，这种自然的神经网络， 6.本研究的目的是揭示嗅觉环境中感觉运动转换的逻辑， 7果蝇运动的调节。核心假设是，就像我们自己的许多日常行为一样，运动的气味调节的控制是分层的。苍蝇的运动是由更简单的元素组成的， 9个运动基元，每个基元持续1-3秒（或10-30步）。气味，而不是作用于 10个瞬时运动参数，如速度和角速度，作用于这些运动基元， 11改变苍蝇执行给定运动原语的概率。这个假设是公式- 12根据我们以前的工作和初步数据。拟议研究的理由是， 13理解气味引导的运动-一种复杂的，灵活的行为-在遗传上易于处理的背景下 14系统将允许精确描绘在感觉运动转换的背景下的步骤。 15自然主义行为。上述假设将通过表征调制的电路基础来测试。 16运动的食物气味使用的技术组合，包括成像，电生理学，定量 17、计算与行为拟议的研究有三个具体目标。1)为了提取原始运动神经- 18个测试和测试的假设，气味调节运动通过改变时间苍蝇花在执行不同的， 19种原始运动。2)为了检验不同的ORN类调节在 20种不同的原始运动者3)阐明侧角在气味调节运动中的作用。重新 21搜索是创新的，因为它采用了复杂的统计工具（分层隐马尔可夫模型， 22 HHMM）和尖端的实验工具，在遗传上易于处理的模式生物的背景下，以获得 23洞察自然主义行为。拟议的研究是重要的，因为它将垂直推进我们的 24理解涉及自然主义行为的感觉运动过程。来自多个领域的见解 25都得出这样的结论：行为被组织成离散的数据包或行为基元。未采取的行动 26倍，通过这些离散包的顺序募集。研究自然行为的一个关键障碍是在大多数情况下，这些离散数据包中存在足够的可变性，使它们无法识别， 28、借助先进的统计工具。通过部署HHMM，我们克服了这一关键障碍。除了代表- 29在我们对自然主义行为的理解上有一个垂直的进步，这是另一个可能的积极结果。 30这项研究是更好的诊断神经条件反射发生通过不正确的行动顺序。 31 32 33