Formation and Development of an Auditory Brainstem Nucleus: the MNTB

听觉脑干核的形成和发育：MNTB

• 批准号: 7998605
• 负责人: Glen Marrs
• 金额: $ 5.77万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7998605
• 关键词: Auditory; Auditory system; Autistic Disorder; Brain; Brain Stem; Cell Nucleus; Characteristics; Data; Development; Embryo; Esthesia; Future; Goals; Hearing; Image; Individual; Investigation; Medial; Morphogenesis; Nature; Nerve; Neurons; Optics; Pattern; Pattern Formation; Phase; Physiological; Physiology; Play; Positioning Attribute; Process; Role; Sensory; Signal Transduction; Synapses; System; Time; Whole-Cell Recordings; postnatal; postsynaptic; public health relevance; research study; sensory system; synaptogenesis

DESCRIPTION (provided by applicant): During embryonic brain development, patterned connectivity, neuronal positioning, and cooperative signaling are established for sensory systems. This temporal window can be utilized to investigate how features of individual synapses relate to function and how neuronal ensembles within and between separate nuclei collectively support sensation. Unfortunately examination of sensory systems during this time period has, for the most part, not been systematically undertaken. The proposed investigations focus upon early development of a conspicuous synaptic connection of the auditory brainstem, the Calyx of Held terminals at the medial nucleus of the trapazoid body (MNTB). Although many details involving neuronal and synaptic physiology at mature connections of the central auditory system have been determined, information regarding embryonic MNTB nucleus formation, initial synaptic connectivity phases, formation of patterning as it relates to auditory function, and onset of functional synaptic signaling at these neurons remains obscure. Through experimental strategies that combine optical recording of morphologic and functional synaptic features with physiologic data from whole-cell recording, initial functional connectivity of this auditory relay will be characterized. These studies will provide fundamental information regarding the nature and timing of early connections that later transform into large, mature nerve terminals. Detailed confocal imaging observations over the developmental period of MNTB formation (embryonic day 14 - postnatal day 4) will identify characteristics and structural patterns of both pre-calyx axonal terminals and postsynaptic MNTB principal neurons. Analysis and quantification of morphologic and functional features of early connections will also yield clues regarding mechanisms that guide MNTB morphogenesis, synaptic formation, and functional input patterning. Finally, the proposed experiments will begin to examine the role that the inhibitory signaling of the GABAergic system plays in guiding the early development and functional patterning of the MNTB. PUBLIC HEALTH RELEVANCE: The proposed experiments will provide a fundamental understanding of how brain connections of a particular auditory system circuit first form at junctions known as synapses, and how these many connections are precisely coordinated during development. The long term goal of these and future studies is to gain a detailed understanding of the process and mechanisms involved in auditory synapse formation to understand how neurons organize into groups and select partners for cooperative signaling that supports normal hearing function. Information gained in this study could be of direct relevance for understanding certain sensory disturbances associated with autism.

描述（由申请人提供）：在胚胎脑发育，图案化连通性，神经元定位和合作信号传导期间，是为感觉系统建立的。可以利用此时间窗口来研究单个突触的特征如何与功能以及在单独的核之间和之间的神经元合奏如何共同支持感觉。不幸的是，在此期间，对感官系统的检查大部分都没有系统地进行。拟议的研究集中于听觉脑干的显着突触连接的早期开发，这是驱动末端的末端的花萼，位于特拉帕动物体（MNTB）的内侧核。尽管已经确定了中央听觉系统成熟连接处的神经元和突触生理的许多细节，但有关胚胎MNTB核形成，初始突触连通性阶段，与听觉功能相关的图案的形成以及这些神经元功能突触信号的发作时的图案的信息仍然是模糊的。通过将形态和功能突触特征的光学记录与全细胞记录的生理数据结合在一起的实验策略，将表征该听觉继电器的初始功能连接。这些研究将提供有关早期联系的性质和时机的基本信息，这些信息随后转化为大型成熟的神经终端。 MNTB形成的发育期（胚胎第14天 - 第4天）的详细共聚焦成像观测将确定腹膜前轴突末端和突触后MNTB主神经元的特征和结构模式。早期连接的形态和功能特征的分析和定量还将产生有关指导MNTB形态发生，突触形成和功能输入图案的机制的线索。最后，提出的实验将开始研究GABA能体系的抑制信号在指导MNTB的早期发展和功能模式中发挥的作用。 公共卫生相关性：拟议的实验将提供对特定听觉系统电路的大脑连接在被称为突触的连接处首次形式的基本理解，以及在开发过程中如何精确地协调了这些许多连接。这些和未来的研究的长期目标是详细了解听觉突触形成所涉及的过程和机制，以了解神经元如何组织成组，并选择合作伙伴以支持正常听力功能的合作信号。在这项研究中获得的信息可能直接相关，以了解与自闭症相关的某些感觉障碍。