Formation and Development of an Auditory Brainstem Nucleus: the MNTB

描述（由申请人提供）：在胚胎脑发育期间，为感觉系统建立了模式连接、神经元定位和协作信号。这个时间窗可以用来研究单个突触的特征如何与功能相关，以及单独的核内和核之间的神经元集合如何共同支持感觉。不幸的是，在这段时间内，对感觉系统的检查在很大程度上还没有系统地进行。拟议的调查集中在早期发展的一个显着的突触连接的听觉脑干，杯举行终端在内侧核的trapazoid体（MNTB）。虽然许多细节涉及神经元和突触生理学在成熟的连接的中央听觉系统已被确定，信息胚胎MNTB核的形成，初始突触连接阶段，形成图案，因为它涉及到听觉功能，和发病的功能性突触信号在这些神经元仍然模糊。通过实验策略，结合联合收割机光学记录的形态和功能的突触功能与生理数据从全细胞记录，最初的功能连接的听觉中继的特点。这些研究将提供有关早期连接的性质和时间的基本信息，这些连接后来转化为大的成熟神经末梢。详细的共聚焦成像观察MNTB形成的发育期（胚胎第14天-出生后第4天）将确定的特点和结构模式的前萼轴突终端和突触后MNTB主要神经元。早期连接的形态和功能特征的分析和量化也将产生关于引导MNTB形态发生、突触形成和功能输入模式的机制的线索。最后，所提出的实验将开始检查GABA能系统的抑制性信号传导在指导MNTB的早期发育和功能模式中所起的作用。 公共卫生相关性：拟议的实验将提供一个基本的理解，一个特定的听觉系统电路的大脑连接如何首先在称为突触的连接处形成，以及这些连接如何在发育过程中精确协调。这些研究和未来研究的长期目标是详细了解听觉突触形成的过程和机制，以了解神经元如何组织成组，并选择支持正常听觉功能的合作信号的合作伙伴。这项研究中获得的信息可能与理解与自闭症相关的某些感觉障碍直接相关。

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.