RoL: FELS: EAGER: Collaborative Research: Exceptions that Test the Rules - Establishing the Feasibility of Avian Feather Muscles as a Study System for Neuromotor Control

RoL：FELS：EAGER：协作研究：测试规则的例外 - 建立鸟类羽毛肌肉作为神经运动控制研究系统的可行性

• 批准号: 1838746
• 负责人: Tobin Hieronymus
• 金额: $ 21.12万
• 依托单位: Northeast Ohio Medical University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2022-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1838746&HistoricalAwards=false
• 关键词: RoL; FELS; EAGER; Collaborative; Research

Nearly all of what is understood about how animals control their movement comes from studies of skeletal muscle under the control of the somatic motor branch of the nervous system - the same kinds of structures that allow humans to walk, grasp objects, and speak. In addition to these systems, animals also control movement with smooth muscle, under the control of the autonomic motor branch of the nervous system - these are the muscles that allow people to sweat, blush, get goosebumps, and move food through the gut. While these are generally considered "low-level" tasks that do not require complex control, birds use autonomic control of smooth muscle in the skin to position feathers for display, and even to control the position of wing feathers in flight. Both of these tasks demand complex integration with other movements. This Rules of Life proposal tests whether there are evolutionarily convergent control systems for smooth muscle and skeletal muscle motor control in bird. The major obstacle to understanding how smooth muscles work in birds is technical. The existing techniques to measure and control skeletal muscle activity cannot be used on smooth muscles. This project will test the use of fiber-optic technology and drug interventions to measure and manipulate smooth muscle function in awake, behaving birds. Investigating the control of smooth muscle in birds can provide a new window into muscle activity. The broader implications of the work extend to the design of control systems, for example those of unmanned autonomous vehicles. In addition to basic research, this project includes teacher training workshops that bring the biology and technology involved into high-school classrooms.The overall objective of this project is to develop methods for recording and manipulating feather muscle activation in vivo. The rationale is that the ability to assess feather muscle activity will open an entirely untapped pool of complex smooth-muscle motor behaviors for comparison to striated-muscle systems. The overall objective will be attained by pursuing two specific aims. First, fiber-optic approaches to record feather muscle activity will be tested in vivo. Smooth muscle activity can currently only be measured reliably in vitro. This set of studies tests the feasibility of fiber photometry with Ca2+-sensitive fluorescent dyes to record the intracellular Ca2+ signaling events that drive muscle contraction in vivo. Second, the molecular basis for modulation and manipulation of feather muscles will be evaluated. Visceral smooth muscles (e.g., wall of gastrointestinal tract) exhibit several pathways that control contractile state, some of which are known to be shared with feather muscles. This set of studies will use expression proteomics to determine the extent of differences in control pathways between feather musculature and visceral smooth muscle, then test indicated control pathway inhibitors to reveal which pathways can be used for targeted manipulation of feather muscle function in vivo.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

几乎所有关于动物如何控制运动的了解都来自于对神经系统躯体运动分支控制下的骨骼肌的研究--这种结构与人类行走、抓住物体和说话的结构相同。除了这些系统，动物还在神经系统自主运动分支的控制下，用平滑的肌肉控制运动--这些肌肉让人流汗、脸红、起鸡皮疙瘩，并通过肠道运输食物。虽然这些通常被认为是不需要复杂控制的低级任务，但鸟类使用皮肤中平滑肌肉的自主控制来定位羽毛以供展示，甚至控制飞行中翅膀羽毛的位置。这两项任务都需要与其他运动进行复杂的整合。这个生命法则提案测试了是否存在进化上收敛的控制系统，用于鸟类的肌肉和骨骼肌运动控制。理解鸟类肌肉是如何工作的主要障碍是技术上的。现有的测量和控制骨骼肌活动的技术不能用于平滑肌肉。该项目将测试使用光纤技术和药物干预来测量和操纵清醒、行为正常的鸟类的平滑肌肉功能。研究鸟类对肌肉的控制可以为了解肌肉活动提供一个新的窗口。这项工作的更广泛影响延伸到控制系统的设计，例如无人自动驾驶车辆的设计。除了基础研究，该项目还包括教师培训讲习班，将所涉及的生物和技术带入高中课堂。该项目的总体目标是开发记录和操纵活体羽毛肌肉激活的方法。其基本原理是，评估羽毛肌肉活动的能力将打开一个完全未被开发的复杂的平滑肌肉运动行为池，用于与横纹肌系统进行比较。总体目标将通过追求两个具体目标来实现。首先，用光纤记录羽毛肌肉活动的方法将在体内进行测试。目前，只有在体外才能可靠地测量平滑肌活动。这组研究测试了使用对钙离子敏感的荧光染料进行纤维光度测量的可行性，以记录在体内驱动肌肉收缩的细胞内钙信号事件。其次，将评估羽毛肌肉调节和操纵的分子基础。内脏平滑肌肉(如胃肠道的壁)展示了几种控制收缩状态的途径，其中一些已知与羽毛肌肉相同。这组研究将使用表达蛋白质组学来确定羽毛肌肉和内脏平滑肌之间控制途径的差异程度，然后测试指示的控制途径抑制剂，以揭示哪些途径可以用于活体中有针对性的操纵羽毛肌肉功能。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。