Mechanisms of sensory neuron morphological diversification, signaling, and functional plasticity

感觉神经元形态多样化、信号传导和功能可塑性的机制

基本信息

批准号：
10654593
负责人：
Piali Sengupta
金额：
$ 79.63万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10654593
关键词：
Adhesions Afferent Neurons Animals Architecture Area Award Behavior Behavior Disorders Behavioral Caenorhabditis elegans Cellular biology Cilia Code Cognition Disorders Collaborations Communication Complex Cues Defect Development Disease Funding Gene Expression Gene Expression Profile Goals Head Individual Lead Modification Morphology National Institute of General Medical Sciences Nematoda Nervous System Neurodevelopmental Disorder Neurons Pathway interactions Pattern Play Process Property Recording of previous events Regulation Research Resolution Role Scientist Sense Organs Sensory Shapes Signal Transduction Stereotyping Structure Temperature Testing Training Translating Variant Work analog behavioral plasticity environmental change experience functional plasticity in vivo innovation insight next generation novel programs public health relevance response sensory mechanism shape analysis synergism

Adhesions Afferent Neurons Animals Architecture Area Award Behavior Behavior Disorders Behavioral Caenorhabditis elegans Cellular biology Cilia Code Cognition Disorders Collaborations Communication Complex Cues Defect Development Disease Funding Gene Expression Gene Expression Profile Goals Head Individual Lead Modification Morphology National Institute of General Medical Sciences Nematoda Nervous System Neurodevelopmental Disorder Neurons Pathway interactions Pattern Play Process Property Recording of previous events Regulation Research Resolution Role Scientist Sense Organs Sensory Shapes Signal Transduction Stereotyping Structure Temperature Testing Training Translating Variant Work analog behavioral plasticity environmental change experience functional plasticity in vivo innovation insight next generation novel programs public health relevance response sensory mechanism shape analysis synergism

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项目摘要

PROJECT SUMMARY The overall goal of our NIGMS-funded research program is to identify and characterize the mechanisms that allow individual sensory neurons to sense and respond to defined environmental cues, and to modulate these responses based on experience and context. The lab explores these issues in two independent but related areas. In the first, we study how individual sensory neuron types acquire their specialized sensory cilia morphologies. In the second, we study how the morphologies and functions of sensory neurons are modulated by experience. With R35 funding, we have been able to build synergies between these research areas and to extend our work in unanticipated directions. A first major goal for the upcoming period will be to build on our work in ciliogenic mechanisms to investigate how the organization of neuronal cilia within a sense organ, as well as interciliary contacts, contribute to shaping sensory neuron functions. We previously showed that sensory cilia are stereotypically organized within a head sense organ in C. elegans; the mechanisms that underlie this organization and the functional consequences of this patterning are unknown. We will determine whether an adhesion code regulates interciliary contacts and organization, and explore how these contacts regulate neuronal communication and function. A second major goal will be to investigate how temperature experience reshapes the complex morphologies of the AFD thermosensory neuron pair in C. elegans. The architecture of the AFD sensory endings is regulated by neuronal activity and plays a critical role in the ability of these neurons to adapt and respond to environmental temperature variations. We will exploit our expertise in neuronal cell biology and high-resolution analyses of sensory behaviors and sensory neuron responses to describe how the shape of the AFD sensory endings is modified as a function of the animal’s experience, and how this modification in turn modulates AFD function. A third major goal will be to investigate how the experience of an analog variable such as temperature is translated into graded gene expression changes in a single sensory neuron type in vivo, and how these gene expression changes in turn influence neuronal properties. We plan to establish whether the gene expression pattern in a neuron encodes its temporal activity history, identify the required regulatory mechanisms, and assess the consequences on neuronal functions. Our multifaceted experimental approach will allow us to generate a comprehensive description of how activity and experience intersect with developmental pathways to modify sensory neuron structure and function, thereby generating appropriate behavioral plasticity. This award will also enable us to continue to train the next generation of scientists, to establish new collaborations, and to generate and test innovative and novel hypotheses. Given the conservation of sensory and ciliogenic mechanisms, we expect that findings from this work will be broadly generalizable, and may provide insights into how altered regulation of neuronal structural and functional plasticity leads to disease.

项目摘要我们由NIGMS资助的研究计划的总体目标是识别和表征其机制允许单个感觉神经元感知并响应定义的环境线索，并调节这些线索基于经验和环境的回应。实验室在两个独立但相关的两个独立区域。首先，我们研究单个感觉神经元类型如何获得其专门的感觉纤毛形态。在第二个中，我们研究了如何调节感觉神经元的形态和功能通过经验。通过R35资金，我们能够在这些研究领域之间建立协同作用将我们的工作扩展到意外的方向。即将到来的时期的第一个主要目标是建立我们的从纤毛生成机制中工作，以调查在有感觉器官中神经元纤毛的组织如何以及内部接触，有助于塑造感觉神经元功能。我们以前表明感觉纤毛是在秀丽隐杆线虫中的头部感官中刻板地组织的。这些机制该组织和该模式的功能后果的基础是未知的。我们将确定粘合剂代码是否调节内部联系和组织，并探讨这些联系方式如何调节神经元的沟通和功能。第二个主要目标是研究温度经验重塑了秀丽隐杆线虫中AFD热感神经元对的复杂形态。这 AFD感觉结局的结构受神经元活动的调节，在能力中起着至关重要的作用这些神经元适应环境温度变化并反应。我们将利用我们的专业知识神经元细胞生物学以及对感觉行为和感觉神经元反应的高分辨率分析描述如何根据动物的经验来修改AFD感官结尾的形状，以及这种修改又如何调节AFD功能。第三个主要目标是研究模拟变量（例如温度）的经验被转化为A中的分级基因表达变化体内单个感觉神经元类型，以及这些基因表达如何变化又影响神经元特性。我们计划确定神经元中的基因表达模式是否编码其临时活性历史记录，确定所需的调节机制，并评估对神经元功能的后果。我们的多方面的实验方法将使我们能够全面描述活动和经验与发展感官神经元结构和功能的发展途径相交产生适当的行为可塑性。该奖项还将使我们能够继续训练下一个产生科学家，建立新的合作，并产生和测试创新和新颖的假设。鉴于感官和纤毛生成机制的保护，我们希望从此发现工作将是可以广泛概括的，并且可以提供有关神经元结构调节的改变的见解功能可塑性导致疾病。