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知识都来自于对骨骼肌的研究，骨骼肌受神经系统躯体运动分支的控制--这类结构使人类能够行走、抓握物体和说话。 除了这些系统，动物还通过平滑肌控制运动，在神经系统的自主运动分支的控制下-这些肌肉允许人们出汗，脸红，起鸡皮疙瘩，并通过肠道移动食物。 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的自主控制来定位羽毛以供展示，甚至在飞行中控制翅膀羽毛的位置。 这两项任务都需要与其他运动进行复杂的整合。 这个生命规则的建议测试是否有进化收敛控制系统的平滑肌和骨骼肌运动控制的鸟类。 了解鸟类平滑肌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。 该项目将测试使用光纤技术和药物干预措施来测量和操纵清醒、行为良好的鸟类的平滑肌功能。 研究鸟类平滑肌的控制可以为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，例如无人驾驶自动驾驶汽车的设计。 除了基础研究之外，该项目还包括教师培训讲习班，将所涉及的生物学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体内羽毛肌肉激活的方法。 其基本原理是，评估羽毛肌活动的能力将打开一个完全未开发的复杂平滑肌运动行为的池，用于与横纹肌系统进行比较。 将通过追求两个具体目标来实现总目标。首先，将在体内测试记录羽毛肌肉活动的光纤方法。平滑肌活性目前只能在体外可靠地测量。 这组研究测试了用Ca2+敏感的荧光染料的纤维光度法记录体内驱动肌肉收缩的细胞内Ca2+信号事件的可行性。其次，羽毛肌肉的调制和操纵的分子基础将进行评估。内脏平滑肌（例如，胃肠道壁）显示出控制收缩状态几种途径，其中一些已知与羽毛肌共享。 这组研究将使用表达蛋白质组学来确定羽毛肌肉组织和内脏平滑肌之间控制途径的差异程度，该奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的支持。影响审查标准。