权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

基本信息

批准号：
9115728
负责人：
Gregory John Gerling
金额：
$ 37.63万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-15 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9115728
关键词：
Ablation Address Aging Apoptosis Architecture BMP4 Behavior Biocompatible Materials Biological Models Biology Biomechanics Body Weight Brain Cells Code Complex Computer Simulation Cues Cutaneous Deoxyuridine Differential Equation Diphtheria Toxin Engineering Environmental Risk Factor Exposure to Face Goals Growth Hair Hair follicle structure Health Human Label Lead Mammals Mechanics Mediating Merkel Cells Modeling Molecular Mus NTF3 gene Neurites Neurobiology Neuronal Plasticity Neurons Neurosciences Organ Organogenesis Peripheral Phase Physiological Property Quantitative Microscopy Ranvier&apos s Nodes Research Rest Sensory Sensory Receptors Shapes Signal Transduction Skin Solid Specific qualifier value Staging Stimulus Structure System Tactile Techniques Testing Texture Thick Tissues Touch sensation Transgenic Mice age related cell type computer studies computerized tools density feeding in vivo innovation interdisciplinary approach morphometry mouse model nerve supply network models neurophysiology neurotransmission novel nutrition object shape receptor research study response social social attachment somatosensory ultraviolet irradiation

项目摘要

DESCRIPTION (provided by applicant): Touch is integral to essential behaviors such as feeding, social bonding and avoiding bodily harm. In mammals, touch is encoded by sensory receptors embedded in the skin. Mammalian skin structure and mechanical properties are dynamic, changing in response to numerous physiological and external conditions, including nutrition, body weight, aging and exposure to environmental factors, such as UV irradiation. Little is known about how these physiologic changes alter neuronal signaling from touch receptors. The objective of this application is to elucidate peripheral mechanisms that govern the firing properties of tactile afferents during normal physiological target-organ changes. The project focuses on mouse slowly adapting type I (SAI) afferents as a model system with unparalleled accessibility for computational and experimental studies. Merkel cells in contact with myelinated cutaneous afferents form gentle-touch receptors that mediate SAI responses. This project is highly relevant to human health because 1) SAI responses in the skin underlie high tactile acuity in humans but little is known about how physiological skin remodeling alters their signaling; and 2) understanding mechanisms of normal neuronal remodeling could identify targets for treating pathological or age-related changes in touch sensitivity. Anatomical studies have shown that skin innervation density changes during normal hair growth in mice. This application will address key open questions: 1) what are the mechanisms that govern innervation changes during hair-follicle cycling, and 2) do changes in innervation lead to altered sensory signaling? The central hypothesis is that structural plasticity of tactile afferents govern touch-evoked firing properties during normal skin remodeling. The hypothesis will be tested with an innovative multidisciplinary approach combining experimental techniques, including neurophysiology, 3D microscopy, quantitative morphometry, tissue biomechanics and novel mouse models, with computational tools such as novel network models of neuronal dynamics, differential equations and solid mechanics. Aims are to 1) define temporal dynamics and cellular mechanisms of neuronal remodeling during skin renewal, 2) analyze the functional consequences of neuronal remodeling on mechanical encoding, and 3) identify the target cell type and candidate molecular cues that drive neuronal remodeling. This project is conceptually innovative because it tackles a novel question in basic neurobiology that is central to the encoding of touch stimuli. Technically innovation lies in its unique, interdisciplinary approaches to combine experimental biology with computational studies to answer these fundamental questions. By identifying mechanisms that govern the reliability of touch-evoked signals in healthy skin, these studies will set the stage to determine how these mechanisms fail in aging and pathophysiological states.

描述（由申请人提供）：触摸是必不可少的基本行为，如喂养，社会联系和避免身体伤害。在哺乳动物中，触觉由嵌入皮肤的感觉受体编码。哺乳动物的皮肤结构和机械特性是动态的，响应于许多生理和外部条件而变化，包括营养、体重、老化和暴露于环境因素，如UV照射。关于这些生理变化如何改变来自触觉感受器的神经元信号，人们知之甚少。本申请的目的是阐明周边机制，管理正常的生理目标器官的变化过程中的触觉传入放电特性。该项目的重点是小鼠缓慢适应I型（SAI）传入作为一个模型系统，具有无与伦比的可访问性的计算和实验研究。默克尔细胞与有髓鞘的皮肤传入神经接触，形成温和的触觉受体，介导SAI反应。该项目与人类健康高度相关，因为1）皮肤中的SAI反应是人类高触觉敏锐度的基础，但对生理皮肤重塑如何改变其信号传导知之甚少; 2）了解正常神经元重塑的机制可以确定治疗触觉敏感性病理或年龄相关变化的目标。解剖学研究表明，在小鼠正常毛发生长期间，皮肤神经支配密度发生变化。这个应用程序将解决关键的开放性问题：1）在毛囊循环过程中，支配神经支配变化的机制是什么？2）神经支配的变化是否会导致感觉信号的改变？中心假设是触觉传入的结构可塑性在正常皮肤重塑过程中控制触摸诱发的放电特性。该假设将通过一种创新的多学科方法进行测试，该方法将实验技术，包括神经生理学，3D显微镜，定量形态测量学，组织生物力学和新型小鼠模型，以及计算工具，如神经元动力学，微分方程和固体力学的新型网络模型。目的是1）定义皮肤更新期间神经元重塑的时间动力学和细胞机制，2）分析神经元重塑对机械编码的功能后果，以及3）识别驱动神经元重塑的靶细胞类型和候选分子线索。这个项目在概念上是创新的，因为它解决了基础神经生物学中的一个新问题，这个问题对触摸刺激的编码至关重要。技术创新在于其独特的跨学科方法，将联合收割机实验生物学与计算研究相结合，以回答这些基本问题。通过确定控制健康皮肤中触摸诱发信号可靠性的机制，这些研究将为确定这些机制在衰老和病理生理状态下如何失效奠定基础。

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Using Force Sensors and Neural Models to Encode Tactile Stimuli as Spike-based Responses.

DOI：
10.1109/haptic.2010.5444657
发表时间：
2010-03-25
期刊：
Proceedings. Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems
影响因子：
0
作者：
Kim EK;Gerling GJ;Wellnitz SA;Lumpkin EA
通讯作者：
Lumpkin EA

Force-Rate Cues Reduce Object Deformation Necessary to Discriminate Compliances Harder than the Skin.

DOI：
10.1109/toh.2017.2715845
发表时间：
2018-04
期刊：
IEEE transactions on haptics
影响因子：
2.9
作者：
Hauser SC;Gerling GJ;Hauser SC;Gerling GJ;Gerling GJ;Hauser SC
通讯作者：
Hauser SC

Optimizing Populations of SAI Tactile Mechanoreceptors to Enable Activities of Daily Living.

DOI：
10.1109/whc.2011.5945461
发表时间：
2011-07-11
期刊：
Proceedings. Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems
影响因子：
0
作者：
Rivest II;Gerling GJ
通讯作者：
Gerling GJ

A DISCRETE-EVENT SIMULATION APPROACH TO IDENTIFY RULES THAT GOVERN ARBOR REMODELING FOR BRANCHING CUTANEOUS AFFERENTS IN HAIRY SKIN.

一种离散事件模拟方法，用于识别多毛皮肤中分支皮肤传入的乔木重塑规则。

DOI：
10.1109/wsc.2017.8247992
发表时间：
2017
期刊：
Proceedings of the ... Winter Simulation Conference. Winter Simulation Conference
影响因子：
0
作者：
Kang,Hyojung;Orlowsky,RachelL;Gerling,GregoryJ
通讯作者：
Gerling,GregoryJ

Natural Variation in Skin Thickness Argues for Mechanical Stimulus Control by Force Instead of Displacement.

皮肤厚度的自然变化支持通过力而不是位移来控制机械刺激。