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: 9274742
• 负责人: Piali Sengupta
• 金额: $ 59.37万
• 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 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274742
• 关键词: Address; Afferent Neurons; Anatomy; Animals; Architecture; Area; Award; Behavior; Behavioral; Caenorhabditis elegans; Cellular biology; Cilia; Cues; Defect; Development; Disease; Environment; Exhibits; Funding; Genetic; Genetic Transcription; Goals; Human; Individual; Investigation; Lead; Mammalian Cell; Mammals; Modality; Molecular; Morphology; National Institute of General Medical Sciences; Nematoda; Nervous system structure; Neuronal Plasticity; Neurons; Organelles; Organism; Pathology; Pathway interactions; Property; Proteins; Research; Research Training; Sensory; Shapes; Signal Transduction; Signaling Molecule; Stimulus; Structure; Temperature; Therapeutic; Work; behavioral response; cell type; experience; functional plasticity; innovation; insight; nervous system disorder; neuron development; neuronal circuitry; neurotransmission; novel; response; sensory mechanism

PROJECT SUMMARY The overall goal of NIGMS-funded research in my lab is to describe the molecular and cellular mechanisms by which individual sensory neuron types acquire their distinctive morphologies and functions, and explore how these properties are further shaped by the animal's experience and environment. In one area, we investigate how sensory neurons in C. elegans elaborate cell type-specific cilia, organelles that house sensory signaling molecules. In a second area, we characterize the mechanisms by which C. elegans exhibits highly sensitive and experience-dependent responses to environmental temperature, a critical but poorly understood sensory modality. These issues are interdependent; neuronal anatomy governs neuronal function, and conversely, neuronal activity shapes neuronal morphology. Integrating these projects will not only allow us to continue our ongoing successful research strategies, but will also enable us to initiate novel avenues of investigation. A first major goal for the next several years is to develop a detailed understanding of the genetic pathways by which ciliary morphological diversity is achieved. Structurally unique cilia are critical for the functions of specific sensory neuron types in multiple species. Although ciliogenic mechanisms are now well-described, how diversity in ciliary structures is generated is unclear. We plan to analyze mechanisms generating ciliary morphological diversity in C. elegans, and also expand our analysis to mammalian cells. A second major goal is to dissect the properties of a class of novel but conserved thermosensory molecules that we recently described, and to explore how these proteins contribute to the extraordinary experience-dependent thermosensitivity of a sensory neuron type. We will also examine how transcriptional and translational changes in single thermosensory neuron types contribute to state- and experience-dependent plasticity in neuronal and circuit properties to alter thermosensory behaviors. A particularly innovative goal is to combine our expertise in neuronal cell biology and analysis of stimulus-evoked sensory responses to systematically describe how sensory activity modulates cilia protein composition and neuronal function, and conversely, explore how cilia architecture dictates sensory neuron response profiles. Under this combined award, we will be able to employ our multifaceted experimental approach to broaden and deepen our analysis of neuronal form and function, incorporate conceptual and experimental innovations to establish new research directions, and provide a more integrative research training experience. Defects in cilia structure and function, as well as altered neuronal signaling and plasticity, underlie a plethora of neurological disorders. Given the extensive conservation of ciliogenic as well as neuronal pathways between mammals and C. elegans, we fully expect that findings from this work will influence and guide related investigations in other organisms in both development and disease.

项目摘要 我实验室的NIGMS资助研究的总体目标是通过以下方式描述分子和细胞机制： 哪些个体感觉神经元类型获得其独特的形态和功能，并探索如何 这些特性进一步由动物的经历和环境塑造。在一个地区，我们调查 C.秀丽线虫精心制作细胞类型特异性纤毛，细胞器，房子的感觉信号 分子。在第二个方面，我们的特点的机制，C。秀丽线虫表现出高度敏感 以及对环境温度的经验依赖性反应，这是一种关键但知之甚少的感觉， 模态这些问题是相互依存的;神经元解剖学支配神经元功能，反之亦然， 神经元活动塑造神经元形态。整合这些项目不仅可以让我们继续我们的 这不仅是我们正在进行的成功的研究战略，而且还将使我们能够启动新的调查途径。第一 未来几年的主要目标是详细了解遗传途径， 实现了纤毛形态多样性。结构独特的纤毛对特定的功能至关重要。 多个物种的感觉神经元类型。虽然纤毛发生机制现在已经得到了很好的描述， 纤毛结构的多样性是不清楚的。我们计划分析产生纤毛的机制， C.形态多样性elegans，并将我们的分析扩展到哺乳动物细胞。第二个主要目标 是剖析一类新的，但保守的热敏分子，我们最近， 描述，并探索这些蛋白质如何有助于非凡的经验依赖 感觉神经元类型的温度敏感性。我们还将研究转录和翻译的变化 在单个热感觉神经元中， 电路特性来改变热敏行为。一个特别创新的目标是联合收割机结合我们的专业知识， 神经元细胞生物学和刺激诱发的感觉反应的分析，以系统地描述如何 感觉活动调节纤毛蛋白质组成和神经元功能，反过来，探索纤毛如何 结构决定了感觉神经元的反应特征。在这一联合奖励下，我们将能够雇用 我们多方面的实验方法，以扩大和深化我们的分析神经元的形式和功能， 结合概念和实验创新，建立新的研究方向，并提供更多的 综合研究培训经验。纤毛结构和功能的缺陷，以及神经元的改变， 信号和可塑性，是大量神经系统疾病的基础。由于广泛的保护， 哺乳动物和C. elegans，我们完全期待， 这项工作将影响和指导其他生物体在发育和疾病方面的相关研究。