CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch

CRCNS:模拟受体排列对接触中尖峰起始的影响

基本信息

项目摘要

DESCRIPTION (provided by applicant): The long-term goal of this research is to determine how mammalian touch receptors transduce forces into neural signals that inform the brain about objects in our dynamic environment. The sense of touch is essential for behaviors that range from avoiding bodily harm to vital social interactions such as child rearing. The touch receptors that innervate the skin are likewise diverse in their peripheral morphologies and physiological outputs. Previous studies demonstrate that different classes of touch receptors produce distinctive firing patterns that encode spatial and temporal features of objects. Despite past progress, the principles that govern neural output in mammalian touch receptors have not been defined. The objective of this application is to elucidate cellular and systems-level mechanisms that generate neural signals in mouse Merkel cell-neurite complexes, which we use as a model for molecular, physiological and computational studies. These complexes mediate slowly adapting type I (SAI) touch responses, which resolve fine spatial details, such as Braille patterns. Our ability to extract edges and object curvature with high speed and fidelity may relate directly to the SAI afferent's distinctive biphasic firing pattern. The SAI afferent's morphology is also unique among touch receptors because it is synaptically coupled to sensory receptor cells. Each SAI afferent has a branching arbor that contacts ~10-40 Merkel cells. The evolutionary maxim 'form follows function' leads to our central hypothesis that the SAI afferent's unique architecture is fundamental to its distinctive firing properties. This new collaborative project will test this hypothesis by combining computational models, microscopy and neurophysiology. We will build novel computational models using solid mechanics, differential equations and statistics to define the key principles that dictate biphasic SAI firing patterns. To inform the modeling, we will elucidate the three dimensional architecture of mouse SAI afferents, including the quantity and arrangement of Merkel cells and action potential initiation zones. The resulting models will make specific predictions about biological mechanisms that underlie touch-evoked responses in mammals. These predictions will then be experimentally tested with neurophysiological recordings from transgenic mice that allow direct visualization of Merkel cells in receptive fields. The intellectual merit of the proposed research lies in our means of joining computational and experimental techniques to determine how touch-receptor anatomy governs physiology. The power of computation allows us to evaluate thousands of possibilities that would be virtually impossible to empirically test one by one. The power of experimental observation allows us to construct realistic models by visualizing specific anatomical structures and molecules, as well as by measuring neuronal outputs. This strategy fits into an emerging paradigm of biological exploration - that of building predictive models to first explore questions in a modeling space and to subsequently test predictions in empirical space. This project is a new venture between researchers in systems engineering and neurobiology whose careers are dedicated to understanding touch. This research proposal describes a new collaborative project that will benefit from infrastructure developed through our recent study of skin mechanics, which resulted in peer-review manuscripts and conference papers [1, 2, 3, 4]. The broader impacts resulting from the proposed research will be to advance the understanding of force transduction mechanisms in biological systems. This project will support teaching and graduate student training in systems engineering, neuroscience and physiology. The biological principles elucidated in this work may further the understanding of neural signaling in other sensory modalities including pain. We expect the models to be critical for engineering artificial touch sensors that can interface with the human nervous system to restore touch sensitivity (e.g., in burn victims and amputees), as well as for applications in human-robotic manipulation in medicine. We expect the experimental results to impact researchers in fields of sensor design, tissue modeling, neurobiology, psychophysics, haptics, and dermatology. Results will be disseminated in appropriate peer-reviewed journals and conference presentations.
描述(由申请人提供):这项研究的长期目标是确定哺乳动物的触觉感受器如何将力转换成神经信号,从而向大脑通报动态环境中的物体。触觉对于从避免身体伤害到重要的社交互动(例如抚养孩子)的行为至关重要。支配皮肤的触觉感受器的外周形态和生理输出也同样多种多样。先前的研究表明,不同类别的触摸感受器会产生独特的放电模式,编码物体的空间和时间特征。尽管过去取得了进展,但控制哺乳动物触觉感受器神经输出的原理尚未确定。该应用的目的是阐明在小鼠默克尔细胞神经突复合物中产生神经信号的细胞和系统级机制,我们将其用作分子、生理和计算研究的模型。这些复合体介导缓慢适应的 I 型 (SAI) 触摸反应,可解析精细的空间细节,例如盲文图案。我们以高速和保真度提取边缘和物体曲率的能力可能与 SAI 传入的独特双相发射模式直接相关。 SAI 传入神经的形态在触觉感受器中也是独一无二的,因为它与感觉感受器细胞突触耦合。每个 SAI 传入神经都有一个分支乔木,可接触约 10-40 个默克尔细胞。进化格言“形式服从功能”引出了我们的中心假设,即 SAI 传入神经的独特架构是其独特发射特性的基础。这个新的合作项目将通过结合计算模型、显微镜和神经生理学来测试这一假设。我们将使用固体力学、微分方程和统计学构建新颖的计算模型,以定义决定双相 SAI 发射模式的关键原理。为了为建模提供信息,我们将阐明小鼠 SAI 传入神经的三维结构,包括默克尔细胞和动作电位起始区的数量和排列。由此产生的模型将对哺乳动物触摸诱发反应的生物机制做出具体预测。然后,这些预测将通过转基因小鼠的神经生理学记录进行实验测试,从而可以直接观察感受野中的默克尔细胞。拟议研究的智力价值在于我们将计算和实验技术结合起来以确定触摸感受器解剖学如何控制生理学。计算的力量使我们能够评估数千种可能性,而这些可能性实际上是不可能通过经验一一测试的。实验观察的力量使我们能够通过可视化特定的解剖结构和分子以及测量神经元输出来构建真实的模型。这种策略适合一种新兴的生物探索范式——构建预测模型,首先探索建模空间中的问题,然后在经验空间中测试预测。该项目是系统工程和神经生物学研究人员之间的一个新项目,他们的职业生涯致力于理解触觉。该研究提案描述了一个新的合作项目,该项目将受益于我们最近对皮肤力学的研究开发的基础设施,该研究产生了同行评审手稿和会议论文 [1,2,3,4]。拟议研究产生的更广泛影响将促进对生物系统中力传导机制的理解。该项目将支持系统工程、神经科学和生理学方面的教学和研究生培训。这项工作阐明的生物学原理可能会进一步理解包括疼痛在内的其他感觉方式中的神经信号传导。我们预计这些模型对于工程人造触摸传感器至关重要,这些传感器可以与人类神经系统接口以恢复触摸灵敏度(例如,烧伤者和截肢者),以及在医学中的人机操纵中的应用。我们预计实验结果将对传感器设计、组织建模、神经生物学、心理物理学、触觉学和皮肤病学领域的研究人员产生影响。结果将在适当的同行评审期刊和会议演讲中传播。

项目成果

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Gregory John Gerling其他文献

Gregory John Gerling的其他文献

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{{ truncateString('Gregory John Gerling', 18)}}的其他基金

NeuronS_MATTR Network: Neuronal & Systems Mechanisms of Affective Touch & Therapeutic Tissue Manipulation Research Network
NeuronS_MATTR 网络:神经元
  • 批准号:
    10612050
  • 财政年份:
    2022
  • 资助金额:
    $ 31.14万
  • 项目类别:
Developing A Quantitative, Multiscale Imaging Approach to Identify Peripheral Mechanisms of Noxious and Innocuous Force Encoding in Mouse Models
开发定量、多尺度成像方法来识别小鼠模型中有害和无害力编码的外围机制
  • 批准号:
    10467144
  • 财政年份:
    2022
  • 资助金额:
    $ 31.14万
  • 项目类别:
Developing A Quantitative, Multiscale Imaging Approach to Identify Peripheral Mechanisms of Noxious and Innocuous Force Encoding in Mouse Models
开发定量、多尺度成像方法来识别小鼠模型中有害和无害力编码的外围机制
  • 批准号:
    10610468
  • 财政年份:
    2022
  • 资助金额:
    $ 31.14万
  • 项目类别:
NeuronS_MATTR Network: Neuronal & Systems Mechanisms of Affective Touch & Therapeutic Tissue Manipulation Research Network
NeuronS_MATTR 网络:神经元
  • 批准号:
    10451081
  • 财政年份:
    2022
  • 资助金额:
    $ 31.14万
  • 项目类别:
Peripheral Mechanisms Governing Tactile Encoding During Normal Target Remodeling
正常目标重塑期间控制触觉编码的外围机制
  • 批准号:
    8741998
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch
CRCNS:模拟受体排列对接触中尖峰起始的影响
  • 批准号:
    8142056
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
Peripheral Mechanisms Governing Tactile Encoding During Normal Target Remodeling
正常目标重塑期间控制触觉编码的外围机制
  • 批准号:
    9115728
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch
CRCNS:模拟受体排列对接触中尖峰起始的影响
  • 批准号:
    8513087
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
Peripheral Mechanisms Governing Tactile Encoding During Normal Target Remodeling
正常目标重塑期间控制触觉编码的外围机制
  • 批准号:
    8630921
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch
CRCNS:模拟受体排列对接触中尖峰起始的影响
  • 批准号:
    8055160
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:

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SCH: INT: Virtual Neuroprosthesis: Restoring Autonomy to People Suffering From Neurotrauma
SCH:INT:虚拟神经假体:恢复神经创伤患者的自主权
  • 批准号:
    9502593
  • 财政年份:
    2017
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    $ 31.14万
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SCH: INT: Virtual Neuroprosthesis: Restoring Autonomy to People Suffering From Neurotrauma
SCH:INT:虚拟神经假体:恢复神经创伤患者的自主权
  • 批准号:
    9974296
  • 财政年份:
    2017
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    $ 31.14万
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SCH: INT: Virtual Neuroprosthesis: Restoring Autonomy to People Suffering From Neurotrauma
SCH:INT:虚拟神经假体:恢复神经创伤患者的自主权
  • 批准号:
    9753215
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    2017
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    $ 31.14万
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CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch
CRCNS:模拟受体排列对接触中尖峰起始的影响
  • 批准号:
    8142056
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
CRCNS: Modeling Impact of Receptor Arrangement on Spike Initiation in Touch
CRCNS:模拟受体排列对接触中尖峰起始的影响
  • 批准号:
    8513087
  • 财政年份:
    2010
  • 资助金额:
    $ 31.14万
  • 项目类别:
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