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

• 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
• 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

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 我们的NIGMS资助的研究计划的总体目标是确定和表征的机制， 允许单个感觉神经元感知和响应定义的环境线索，并调节这些线索 基于经验和背景的反应。该实验室在两个独立但相关的领域探索这些问题。 地区首先，我们研究了单个感觉神经元类型如何获得其专门的感觉纤毛 形态学第二部分，我们研究了感觉神经元的形态和功能是如何被调节的 凭经验有了R35资金，我们能够在这些研究领域之间建立协同效应， 将我们的工作扩展到意想不到的方向。下一个时期的第一个主要目标将是在我们的基础上， 研究纤毛发生机制，以研究感觉器官内神经元纤毛的组织，如 以及睫状体间接触，有助于形成感觉神经元功能。我们之前已经证明， 感觉纤毛在C. elegans; the mechanisms机制that 这种模式的功能后果是未知的。我们将确定 粘附代码是否调节睫状体间的接触和组织，并探讨这些接触如何 调节神经元的通讯和功能。第二个主要目标是研究温度 经验重塑了C.优雅的的 AFD感觉末梢的结构受神经元活动的调节，并在神经元活动的能力中起着关键作用。 这些神经元适应和响应环境温度的变化。我们将利用我们的专业知识， 神经元细胞生物学和感觉行为的高分辨率分析和感觉神经元对 描述AFD感觉末梢的形状如何根据动物的经验进行修改，以及 这种改变如何反过来调节AFD功能。第三个主要目标将是调查 类似变量如温度的经验被翻译成基因表达的分级变化， 体内单个感觉神经元类型，以及这些基因表达变化如何反过来影响神经元 特性.我们计划确定神经元中的基因表达模式是否编码其时间活动 历史，确定所需的调节机制，并评估对神经元功能的影响。我们 多方面的实验方法将使我们能够产生一个全面的描述， 经验与发育途径相交，以改变感觉神经元的结构和功能，从而 产生适当的行为可塑性。这个奖项也将使我们能够继续培养下一个 新一代的科学家，建立新的合作，并产生和测试创新和新颖的 假设考虑到感觉和纤毛发生机制的保守性，我们希望这项研究的结果 工作将是广泛的推广，并可能提供洞察如何改变调节神经元结构， 和功能可塑性导致疾病。