Developmental Determination of Central Auditory Physiology by the Inner Ear
内耳中枢听觉生理学的发育决定
基本信息
- 批准号:10365728
- 负责人:
- 金额:$ 36.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AblationAcoustic NerveAddressAnatomyAnimalsApoptoticArchitectureAuditoryAuditory PhysiologyAuditory systemBasilar PapillaBiophysicsBirdsBrainBrain StemBrain regionCell NucleusCharacteristicsChickCochleaCochlear nucleusCuesDataDependenceDevelopmentEarEarly InterventionElectrophysiology (science)EmbryoEpithelialExhibitsFailureFrequenciesGeneticGoalsHair CellsHealthHearingHearing problemHumanInstructionInterventionInvestigationIon ChannelKnowledgeLabyrinthMammalsMapsMethodsMissionModelingMolecularMorphologyNational Institute on Deafness and Other Communication DisordersNeuraxisNeuronsPathway interactionsPatternPeripheralPhenotypePhysiologyPopulationProcessPropertyResearchRoleSensorySignal TransductionSourceStructureSynapsesSystemTestingTherapeuticTherapeutic InterventionTimeWorkbasebone morphogenic proteinchildhood hearing losschordincochlear developmentcritical perioddeafdeafeningdeafnessexperimental studygenetic manipulationhearing impairmenthearing preservationinnovationinsightjuvenile animalmorphogensnerve supplyneural patterningneurodevelopmentneuron lossotoconiaoverexpressionpreservationrelating to nervous systemresponsesoundtool
项目摘要
Project Summary:
A longstanding and fundamental question of neural development in sensory pathways is: What is the
role of the organization of the sensory epithelium in establishing central topographic organization? In the
auditory system a direct approach to addressing this question has been elusive because it has not been
possible to manipulate the input to the brain from the auditory periphery without either complete ablation of the
inner ear or induction of hearing dysfunction. The proposed experiments will establish for the first time, a model
of repatterned frequency representation in the chick inner ear by utilizing a new genetic manipulation in
embryos. This manipulation takes advantage of the known genetic factors that establish the organization of the
ear at a very early developmental stage that precedes the auditory nerve innervation of the central nervous
system. By overexpressing one of these factors, bone morphogenic protein 7 (BMP7), inner ears develop
almost exclusively low frequency hair cell phenotypes. In the first brain structure to receive auditory nerve
input, the cochlear nucleus, neurons express a number of well characterized biophysical and morphological
specializations for processing sound in specific frequencies. Frequency specific tuning is topographically
mapped in both the ear and auditory brain regions, a feature known as 'tonotopy.' Thus, neural specialization
occurs along an orderly tonotopic map in the cochlear nucleus. The central hypothesis of this proposal is that
tonotopic refinement of specializations in the cochlear nucleus is developmentally determined by patterned
input from the inner ear, and is not independently induced by local cues in the developing brain. This
hypothesis is now testable using animals with tonotopically altered inner ears. The first aim of this proposal is
to examine whether the BMP7 manipulation indeed induces repatterning of hair cell tuning mechanism in the
inner ear. The second aim investigates the electrical input response properties of cochlear nucleus neurons in
animals that have developed with tonotopically altered inner ears. Finally, the third aim will investigate the
dependence of cochlear nucleus structure on normal topographic innervation from the auditory nerve. These
research objectives, if successful, will provide new insights into the mechanisms that establish the functional
organization of auditory structures. Revelation of these mechanisms may be informative to optimization
strategies for therapeutic interventions in early deafness or hearing loss that aim to preserve normal function
and capacity in auditory circuitry.
项目概要:
感觉通路中神经发育的一个长期存在的基本问题是:
感觉上皮的组织在建立中央地形组织中的作用?在
听觉系统直接解决这个问题的方法一直难以捉摸,因为它还没有
可以操纵从听觉外围到大脑的输入,而无需完全消融听觉外围。
内耳或诱发听力障碍。拟议的实验将首次建立一个模型,
利用一种新的遗传操作,
胚胎这种操纵利用了已知的遗传因素,这些遗传因素建立了细胞的组织结构。
在听觉神经支配中枢神经之前的非常早期的发育阶段的耳朵
系统通过过度表达这些因子之一,骨形态发生蛋白7(BMP7),内耳发育
几乎完全是低频毛细胞表型。在第一个接受听觉神经的大脑结构中
输入,耳蜗核,神经元表达了许多良好的生物物理和形态特征,
专门处理特定频率的声音。频率特定调谐是地形学上
在耳朵和听觉大脑区域都有映射,这一特征被称为“音调映射”。因此,神经特化
沿着耳蜗核中有序的音调分布图发生。该提案的中心假设是,
耳蜗核中特化的音调定位细化是由模式化的
输入来自内耳,并且不是由发育中的大脑中的局部线索独立诱导的。这
这一假说现在可以用内耳音调改变的动物来验证。这项建议的第一个目的是
为了检查BMP 7的操作是否确实诱导了毛细胞调谐机制的重新模式化,
内耳第二个目的是研究耳蜗核神经元的电输入反应特性。
内耳发育成音调改变的动物。最后,第三个目标将调查
耳蜗核结构对听神经正常局部神经支配的依赖性。这些
研究目标,如果成功的话,将提供新的见解,建立功能的机制,
听觉结构的组织。揭示这些机理对优化设计具有一定的指导意义
旨在保护正常功能的早期耳聋或听力损失的治疗干预策略
和听觉回路的能力。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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R. Michael Burger其他文献
Development and Function of Inhibitory Circuitry in the Avian Auditory Brainstem
禽听觉脑干抑制电路的发育和功能
- DOI:
10.1007/978-3-319-21530-3_5 - 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
R. Michael Burger - 通讯作者:
R. Michael Burger
Evaluation of UVB reduction by materials commonly used in reptile husbandry.
爬行动物饲养中常用材料减少 UVB 的评估。
- DOI:
- 发表时间:
2007 - 期刊:
- 影响因子:1.3
- 作者:
R. Michael Burger;W. Gehrmann;G. Ferguson - 通讯作者:
G. Ferguson
R. Michael Burger的其他文献
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{{ truncateString('R. Michael Burger', 18)}}的其他基金
Developmental Determination of Central Auditory Physiology by the Inner Ear
内耳中枢听觉生理学的发育决定
- 批准号:
10610316 - 财政年份:2022
- 资助金额:
$ 36.73万 - 项目类别:
Efferent inhibitory mechanisms in binaural processing
双耳处理中的传出抑制机制
- 批准号:
7769546 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别:
Efferent inhibitory mechanisms in binaural processing
双耳处理中的传出抑制机制
- 批准号:
8413054 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别:
Efferent inhibitory mechanisms in binaural processing
双耳处理中的传出抑制机制
- 批准号:
7654486 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别:
Efferent inhibitory mechanisms in binaural processing
双耳处理中的传出抑制机制
- 批准号:
8020976 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别:
Efferent inhibitory mechanisms in binaural processing
双耳处理中的传出抑制机制
- 批准号:
8213448 - 财政年份:2009
- 资助金额:
$ 36.73万 - 项目类别: