HEARING: DEVELOPMENT OF SYNAPTIC CIRCUITS

听力：突触回路的发育

• 批准号: 6626887
• 负责人: CRAIG K HENKEL
• 金额: $ 29.48万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-15 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626887
• 关键词: auditory pathways; developmental neurobiology; dyes; ferrets; fiber cell; hearing; inferior colliculus; mammalian embryology; neuroimaging; synaptogenesis; video microscopy

DESCRIPTION: The present application will study development of ascending projections that terminate within the inferior colliculus in non-overlapping or only partially overlapping patterns of bands and patches. Bands of afferent termination represent a vertical segregation across the thickness of the fibrodendritic layers of the inferior colliculus and patches represent a horizontal segregation along the plane of the layers. It is not known whether these patterns are established as the afferent fibers first enter the inferior colliculus or whether they form secondarily from an initial overlap. Nevertheless these afferent patterns, together with the parallel fibrodendritic architecture of the inferior colliculus, determine the synaptic interactions that take place within the nucleus. In order to understand how neural circuits involved in information processing develop, the proposed studies will identify 1) the spatial and temporal characteristics of arrival, distribution and refinement of afferent projections, 2) the relationship of those events to synaptogenesis and 3) the mechanisms that govern the formation of the pattern of afferent termination within the layers. Specifically, experiments will address these issues by studying the development of the ascending projections to the inferior colliculus from the lateral superior olive (LSO) and dorsal nucleus of the lateral lemniscus (DNLL) in an altricial mammal, the ferret. The position and distribution of the LSO and DNLL axons projecting to the inferior colliculus will be studied in a normal developmental series of ferret kits and an experimental series with cochlear ablations. Lipophilic carbocyanine dyes, DiI and DiD, will be used to label the ipsilateral and contralateral LSO and the commissure of DNLL fibers. In addition, the distribution of synaptic contacts along the tonotopic axis and parallel to the fibrodendritic layers will be sampled at developmental time points determined from the tracing studies. Knowledge of the development of afferent projections to the inferior colliculus, and the integrative circuits that ultimately result, is critical in understanding auditory functions that may be at risk due to genetic anomaly, nutritional imbalance, effects of teratogens during pregnancy or perhaps even to premature birth. While subsequent auditory experience may alter intrinsic auditory circuits, the initial construction of functional circuits remains fundamental to understanding neural and behavioral plasticity that may lead to rational intervention and treatment outcomes.

描述：本申请将研究上升的发展。 在下丘内终止的投射不重叠或 只有部分重叠的条带和斑块图案。传入神经束 终端表示在厚度上的垂直分离 下丘和斑块的纤维树突层代表 沿层平面的水平偏析。目前还不清楚是否 这些模式是在传入纤维首先进入下半部时建立的 小丘或它们是否从最初的重叠中形成。 然而，这些传入模式与平行的纤维树突一起 下丘的构筑，决定突触的相互作用 这发生在原子核内。为了了解神经回路是如何 参与信息处理的开发，建议的研究将确定 1)到达、分布和分布的时空特征 改进传入预测，2)这些事件与 突触发生和3)支配模式形成的机制 各层内的传入终末。具体地说，实验将 通过研究上升投影的发展来解决这些问题 从外侧上橄榄(LSO)和背侧至下丘 雪貂的外侧丘疹核(DNLL)。这个 LSO和DNLL轴突投射到下侧的位置和分布 将在雪貂的正常发育系列中研究丘脑和 一系列实验性的人工耳蜗术。亲脂性碳菁染料， DII和DID将用于标记同侧和对侧LSO和 DNLL纤维的连合。此外，突触的分布 沿张力轴和平行于纤维树突层的接触 将在根据跟踪确定的发育时间点进行采样 学习。对下位者的传入投射发展的认识 丘脑，以及最终导致的整合电路，在 了解可能因遗传异常而面临风险的听觉功能， 营养失衡，怀孕期间或甚至是致畸因素的影响 到早产。而随后的听觉体验可能会改变固有的 听觉电路，最初的功能电路结构仍然存在 了解神经和行为可塑性的基础，这可能会导致 合理的干预和治疗结果。