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

项目总结 我们NIGMS资助的研究计划的总体目标是识别和表征 允许单个感觉神经元感知并对特定的环境线索做出反应，并对其进行调节 基于经验和背景的回应。该实验室在两个独立但相关的问题上探索了这些问题 区域。首先，我们研究不同类型的感觉神经元是如何获得其特殊的感觉纤毛的。 形态特征。在第二部分，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的资金，我们已经能够在这些研究领域之间建立协同效应，并 在意想不到的方向上扩展我们的工作。下一阶段的第一个主要目标将是在我们的 研究纤毛发生机制，研究感觉器官内神经元纤毛的组织，如 以及睫状接触，有助于塑造感觉神经元功能。我们之前已经证明了 在线虫中，感觉纤毛通常是在头部感觉器官内组织起来的； 这一组织的基础和这种模式的功能后果尚不清楚。我们将决定 附着性代码是否规范纤毛接触和组织，并探索这些接触是如何 调节神经元的通讯和功能。第二个主要目标将是研究温度如何 经验重塑了线虫AFD热敏神经元对的复杂形态。这个 AFD感觉末梢的结构受神经元活动的调节，并在能力中发挥关键作用 这些神经元对环境温度变化做出适应和反应。我们将利用我们的专业知识在 神经细胞生物学和感觉行为和感觉神经元反应的高分辨率分析 描述AFD感官末端的形状如何根据动物的经验进行修改，以及 这种修饰是如何反过来调节AFD功能的。第三个主要目标将是调查 温度等模拟变量的经验转化为基因表达的分级变化 体内单个感觉神经元类型，以及这些基因的表达变化如何反过来影响神经元 属性。我们计划确定神经元中的基因表达模式是否编码了它的时间活动 病史，确定所需的调节机制，并评估对神经元功能的影响。我们的 多方面的实验方法将使我们能够全面描述活动和 经验与改变感觉神经元结构和功能的发育途径相交，从而 产生适当的行为可塑性。这一奖项也将使我们能够继续培训下一位 一代科学家，建立新的合作，产生和测试创新和新颖的东西 假设。考虑到感觉和纤毛形成机制的保守性，我们预计这一发现 这项工作将具有广泛的普遍性，并可能为如何改变神经元结构的调节提供见解。 而功能可塑性会导致疾病。

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.