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Neuromodulatory Control of Switching between Single and Dual Oscillatory Network States

单和双振荡网络状态之间切换的神经调节控制

基本信息

批准号：
1755283
负责人：
Dawn Blitz
金额：
$ 36.02万
依托单位：
Miami 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：
2018-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755283&HistoricalAwards=false
关键词：
Neuromodulatory Control Switching between Single

项目摘要

Networks of neurons are important for rhythmic behaviors such as walking, breathing, and chewing, as well as cognitive processes such as learning and memory. Flexibility of these rhythmic networks is essential for organisms to alter their behavioral output to meet changing demands. An important aspect of network flexibility is that neurons can rapidly switch their participation between networks. Modulatory inputs that project to rhythmic networks can induce neuronal switching through the release of chemical messengers. These chemical messengers alter network activity through their modulatory actions on the properties of neurons and on the synaptic connections between neurons. Determining how individual modulatory actions combine to elicit switching is a major challenge in the field of neuroscience. Small well-defined networks are instrumental in bridging the gap between cellular-level actions and whole network output. In particular, the crustacean stomatogastric nervous system (STNS) provides access to all network components as well as modulatory inputs to networks, and enables manipulation of individual neuronal properties and synaptic connections. This proposal uses the STNS to identify fundamental cellular mechanisms by which modulatory inputs switch neuronal participation between rhythmic networks. This includes the use of hybrid biological-computational networks to dissect the contributions of individual modulatory actions. This project also advances scientific discovery and learning for graduate and undergraduate students through training in the research lab of the principal investigator and in advanced lab-based courses. Underrepresented groups continue to be incorporated into the lab's research through partnerships with university and elementary school level STEM minority participation programs. Interestingly, neuronal switching can include neurons that switch between single and dual network activity. This switching can result in a single neuron expressing two activity patterns at two different frequencies. There is some evidence that modulatory inputs can elicit switching through their actions on synapses and neuronal properties. However, the complex interplay of electrical coupling, chemical synapses, and neuronal membrane properties has limited research at the network level. An identified modulatory input in the STNS causes a neuron to partially decouple from its electrically coupled partners in one network and simultaneously participate in a second network. The objectives of this proposal are to determine how modulatory actions, individually and collectively, regulate switching between a single and a dual network state. These objectives are achieved using a combination of electrophysiological and computational approaches, including hybrid networks in which biological and model neurons are coupled with the dynamic clamp technique. This project aims to identify novel mechanisms by which modulatory actions enable a neuron to become an active contributor to: 1) rhythm generation for two rhythms simultaneously, despite their occurrence at different frequencies, and 2) coordination among different network neurons. Determining these mechanisms will provide new insights into how electrical and chemical synapses can interact with neuronal membrane properties to regulate participation between networks. Increased understanding of how electrical coupling interacts with other network properties also provides a framework for future biological and computational studies in other rhythmic neural networks including those in larger, less accessible systems.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.

神经元网络对于行走、呼吸和咀嚼等有节奏的行为以及学习和记忆等认知过程都很重要。这些节律网络的灵活性对于生物体改变其行为输出以满足不断变化的需求至关重要。网络灵活性的一个重要方面是神经元可以在网络之间快速切换它们的参与。投射到节律网络的调节性输入可以通过释放化学信使诱导神经元转换。这些化学信使通过调节神经元的性质和神经元之间的突触连接来改变网络活动。确定个体调节动作如何结合联合收割机以引起转换是神经科学领域的一个主要挑战。小型定义明确的网络有助于弥合细胞级行动和整个网络输出之间的差距。特别是，甲壳类动物的口胃神经系统（STNS）提供了访问所有的网络组件以及调制输入网络，并使操纵个别神经元的属性和突触连接。该建议使用STNS来确定基本的细胞机制，通过该机制调节输入在节律网络之间切换神经元参与。这包括使用混合生物计算网络来剖析个体调节作用的贡献。该项目还通过在主要研究者的研究实验室和高级实验室课程中进行培训，促进研究生和本科生的科学发现和学习。代表性不足的群体继续通过与大学和小学STEM少数民族参与计划的合作伙伴关系纳入实验室的研究。有趣的是，神经元切换可以包括在单网络活动和双网络活动之间切换的神经元。这种转换可以导致单个神经元以两种不同的频率表达两种活动模式。有一些证据表明，调制输入可以通过其对突触和神经元特性的作用引起开关。然而，电耦合，化学突触和神经元膜特性的复杂相互作用限制了网络水平的研究。在STNS中识别的调制输入导致神经元与其在一个网络中的电耦合伙伴部分解耦，并同时参与第二个网络。这个建议的目标是确定如何调节行动，单独和集体，调节单和双网络状态之间的切换。这些目标是使用电生理学和计算方法的组合来实现的，包括生物和模型神经元与动态钳技术相结合的混合网络。该项目旨在确定新的机制，通过这些机制，调节作用使神经元成为一个积极的贡献者：1）同时产生两种节奏的节奏，尽管它们发生在不同的频率，2）不同网络神经元之间的协调。确定这些机制将为电突触和化学突触如何与神经元膜特性相互作用以调节网络之间的参与提供新的见解。对电耦合如何与其他网络特性相互作用的进一步理解也为其他节律神经网络的未来生物学和计算研究提供了一个框架，包括那些更大，更难进入的系统。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。