Collaborative Research: Diversity of modulation and functional flexibility in small neuronal networks: An evolutionary and mechanistic approach

合作研究：小神经元网络中调制的多样性和功能灵活性：进化和机械方法

• 批准号: 2128484
• 负责人: David Schulz
• 金额: $ 37.21万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2128484&HistoricalAwards=false
• 关键词: Collaborative; Research; Diversity; modulation; functional

Rhythmic movements, such as heartbeat and locomotion, must be flexible to allow animals to alter their behavior in response to changing conditions. Rhythmic movements are controlled by networks of nerve cells that interact with one another to produce patterns of nerve impulses that drive appropriate muscle movements. To alter movement patterns, these neural networks rely on the actions of chemical compounds called neuromodulators; these compounds alter (modulate) the properties and interactions of the cells in the network, thereby enabling them to alter the pattern of movements that are generated by the network. Such alterations include, for example, changes in the speed of the resulting behavior or the coordination of muscles that control different portions of the movement pattern. There is evidence, however, that the extent to which similar networks can be altered ("modulatory capacity") varies among species. This project addresses two fundamental questions related to this variability in modulatory capacity: first, on an evolutionary timescale, what variables determine the extent to which networks can be modulated, and second, what factors/mechanisms underlie differences in modulatory capacity. In addition to addressing these questions using as exemplars the stomatogastric network and the cardiac network in a crab that eats only kelp versus a crab that eats many different kinds of food, the current project also prepares the next generation of scientists by (1) training high school students and undergraduates in a variety of research techniques, as well as in designing experiments and in analyzing and presenting data, and (2) providing continuity and potential expansion of the neuroscience component of a program that engages 7th grade Native Americans in Maine in science to enhance their educational aspirations and success in high school and beyond.This project uses the stomatogastric and cardiac networks of closely related majoid crab species with vastly different dietary diversity to test the hypothesis that modulatory capacity is an important evolutionary substrate for diversity within any given behavior, and to ask what mechanisms underlie differences in modulatory capacity. Current data suggest that the stomatogastric network in Pugettia producta, a species that eats only kelp, is not responsive to many modulators that alter the network in another majoid, Libinia emarginata, which has a highly diverse diet. This project expands the number of neuromodulators tested, as well as examines and compares modulation of the cardiac network in the same species. The investigators use transcriptomics and mass spectrometry to identify native isoforms of peptide modulators in these majoids, then use physiological recordings to compare the modulatory capacities of the Pugettia and Libinia stomatogastric and cardiac neuromuscular systems. The prediction is that modulatory capacity in the Pugettia stomatogastric system is less than that of the opportunistic feeder, but that modulation in systems that are presumably subject to similar demands for flexibility, e.g., the cardiac neuromuscular system, is not markedly different. To examine the mechanisms that underlie changes in modulatory capacity, the investigators use transcriptomics, testing the hypothesis that the mechanism underlying decreased modulatory capacity of the Pugettia stomatogastric system is an absence or decreased abundance of receptors to those modulators. Transcriptomics results are confirmed using qRT-PCR and through expression of the receptors of the two species to compare relative binding affinities.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.

有节奏的运动，如心跳和运动，必须是灵活的，以允许动物改变他们的行为，以应对不断变化的条件。有节奏的运动是由神经细胞网络控制的，这些神经细胞网络相互作用，产生神经冲动模式，驱动适当的肌肉运动。为了改变运动模式，这些神经网络依赖于称为神经调节剂的化合物的作用;这些化合物改变（调节）网络中细胞的特性和相互作用，从而使它们能够改变网络产生的运动模式。这样的改变包括，例如，所产生的行为的速度或控制运动模式的不同部分的肌肉的协调的变化。然而，有证据表明，类似网络可以改变的程度（“调节能力”）因物种而异。该项目解决了两个基本问题，这种可变性的调节能力：第一，在进化的时间尺度上，什么变量决定在何种程度上可以调节网络，第二，什么因素/机制的调节能力的差异。除了以只吃海带的螃蟹与吃多种不同食物的螃蟹的胃网络和心脏网络为例来解决这些问题外，目前的项目还通过以下方式为下一代科学家做好准备：（1）培训高中生和大学生掌握各种研究技术，以及设计实验和分析和展示数据，以及（2）提供连续性和潜在的扩展的神经科学组成部分的一个计划，从事7年级的美洲原住民在缅因州在科学，以提高他们的教育愿望和成功，在高中及以后。该项目使用的口胃和心脏网络密切相关的majoid蟹物种有很大的饮食多样性，以测试假设，即调节能力是一个重要的进化基质的多样性在任何给定的行为，并问什么机制的差异调节能力。目前的数据表明，Pugettia producta（一种只吃海带的物种）的口胃网络对许多调节剂没有反应，这些调节剂改变了另一种具有高度多样化饮食的majoid，Libinia embryata的网络。该项目扩大了测试的神经调质的数量，并检查和比较了同一物种中心脏网络的调制。研究人员使用转录组学和质谱来识别这些majoids中肽调节剂的天然亚型，然后使用生理记录来比较Pugettia和Libinia口胃和心脏神经肌肉系统的调节能力。预测是Pugettia口胃系统的调节能力小于机会性喂食器的调节能力，但是在可能受到类似灵活性需求的系统中的调节，例如，心脏神经肌肉系统没有明显的不同。为了研究调节能力变化的机制，研究人员使用转录组学，检验以下假设：Pugettia口胃系统调节能力降低的机制是这些调节剂的受体缺乏或丰度降低。转录组学结果通过qRT-PCR和两个物种受体的表达来确认，以比较相对结合亲和力。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。