Dendritic Integration and Synaptic Plasticity in the MSO
MSO 中的树突整合和突触可塑性
基本信息
- 批准号:10316175
- 负责人:
- 金额:$ 43.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-07-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAblationAcousticsAction PotentialsAddressAffectAgreementAnatomyAntibodiesAreaAuditoryAuditory ProsthesisAxonBinauralBirdsBrainBrain StemCaliberCell NucleusCellsChildClinicalClosure by clampCochleaCodeCuesDataDendritesDetectionDevelopmentDevelopmental ProcessEarElectrophysiology (science)EnvironmentExhibitsFire - disastersFluorescenceFoundationsFrequenciesGenerationsGerbilsGoalsHearingHumanIn VitroInjectionsIon Channel GatingLanguage DevelopmentLateralLightLightingLocationMammalsMeasuresMedialMembraneModelingMorphologyNeuronsOpticsOutcomes ResearchPatternPhenotypePhysiologicalPlayPositioning AttributePotassium ChannelProcessPropertyResearchResolutionRoleSensorineural Hearing LossShapesSliceSodium ChannelSound LocalizationSpeechSpeech DiscriminationSpeech PerceptionStimulusStructureSynaptic plasticityTestingTimeVariantbasebinaural hearingbiophysical propertiescell typechannel blockersdeafnessdensityelectrical propertyexperienceexperimental studyhearing impairmention channel blockerlarge datasetsmedial superior oliveneural patterningneuronal cell bodynormal hearingpatch clampreceptive fieldsoundtheoriesvoltagevoltage clampvoltage gated channel
项目摘要
Project Summary
Humans and other mammals use the temporal fine structure in sounds to identify and help
localize auditory objects in three-dimensional space. The broad goal of this research is both to
understand how sound localization cues are processed in the brain as well as to understand how
neurons in the underlying circuitry acquire the appropriate biophysical properties during development.
This proposal focuses on the medial superior olive (MSO), the first and critical stage for processing
interaural time differences (ITDs) from the two ears, cues that are used for horizontal sound localization
as well as for understanding speech patterns in noisy environments. ITDs are computed in the MSO via
the process of coincidence detection, in which the simultaneous arrival of excitatory inputs from the two
ears is detected and conveyed through action potential firing with a time resolution of a few tens of
microseconds.
The neurons of the MSO have historically been assumed to be functionally and morphologically
homogeneous. However, our preliminary data refutes this simplistic view of the MSO: we hypothesize
instead that variation in dendritic morphology and electrical properties critically shapes the location of
spatial receptive fields, and that these differences are in part influenced after hearing onset by the level
and pattern of neural activity. We will address these questions by combining paired dendritic and somatic
patch recordings, compartmental modeling, patterned LED illumination of light-sensitive channel
blockers, and hearing manipulations. Aim 1 will address the functional significance of the newly
discovered tonotopic diversity in electophysiological properties of MSO neurons both in vitro using patch-
clamp recordings. Aim 2 will extend these analyses to understand how the functional diversity in MSO
neurons is conferred by differences in the expression levels and properties of voltage-gated channels in
the axon initial segment. Aim 3 will explore how the diversity of dendritic structure itself shapes the
temporal requirements for optimal detection of binaural coincidence.
The information from these experiments will increase our understanding of the mechanisms
underlying spatial hearing in mammals, as well as the developmental processes that control the
formation of a critical circuit component in the MSO. As binaural hearing is important for speech
perception and language acquisition in children, a mechanistic understanding of binaural circuit function
and development may ultimately inform clinical strategies for addressing hearing impairments.
项目概要
人类和其他哺乳动物利用声音中的时间精细结构来识别和帮助
在三维空间中定位听觉对象。这项研究的总体目标是
了解声音定位线索在大脑中的处理方式以及如何
底层电路中的神经元在发育过程中获得适当的生物物理特性。
该提案重点关注内侧上橄榄 (MSO),这是加工的第一个也是关键的阶段
两耳的耳间时间差 (ITD),用于水平声音定位的提示
以及理解嘈杂环境中的语音模式。 ITD 在 MSO 中通过以下方式计算
重合检测的过程,其中来自两个的兴奋性输入同时到达
耳朵通过动作电位发射进行检测和传达,时间分辨率为几十
微秒。
MSO 的神经元历来被认为在功能和形态上
同质。然而,我们的初步数据驳斥了 MSO 的这种简单化观点:我们假设
相反,树突形态和电性能的变化关键地决定了
空间感受野,并且这些差异在听力开始后部分受到水平的影响
和神经活动模式。我们将通过结合成对的树突状细胞和体细胞来解决这些问题
斑块记录、区室建模、光敏通道的图案化 LED 照明
阻滞剂和听力操纵。目标 1 将解决新的功能意义
使用贴片在体外发现了 MSO 神经元电生理特性的音调多样性
钳位录音。目标 2 将扩展这些分析,以了解 MSO 中的功能多样性如何
神经元的差异是由电压门控通道的表达水平和特性的差异决定的。
轴突起始段。目标 3 将探索树突结构本身的多样性如何塑造
双耳重合最佳检测的时间要求。
这些实验的信息将增加我们对机制的理解
哺乳动物的潜在空间听觉,以及控制听觉的发育过程
MSO 中关键电路组件的形成。由于双耳听力对于言语很重要
儿童的感知和语言习得,双耳回路功能的机械理解
发展可能最终为解决听力障碍的临床策略提供信息。
项目成果
期刊论文数量(15)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
In vivo coincidence detection in mammalian sound localization generates phase delays.
- DOI:10.1038/nn.3948
- 发表时间:2015-03
- 期刊:
- 影响因子:25
- 作者:Franken, Tom P.;Roberts, Michael T.;Wei, Liting;Golding, Nace L.;Joris, Philip X.
- 通讯作者:Joris, Philip X.
Glycinergic Inhibitory Plasticity in Binaural Neurons Is Cumulative and Gated by Developmental Changes in Action Potential Backpropagation.
双耳神经元中的甘氨酸能抑制可塑性是累积的,并由动作电位反向传播的发育变化控制。
- DOI:10.1016/j.neuron.2018.03.001
- 发表时间:2018
- 期刊:
- 影响因子:16.2
- 作者:Winters,BradleyD;Golding,NaceL
- 通讯作者:Golding,NaceL
An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision.
- DOI:10.1523/jneurosci.3882-11.2012
- 发表时间:2012-02-22
- 期刊:
- 影响因子:0
- 作者:Khurana S;Liu Z;Lewis AS;Rosa K;Chetkovich D;Golding NL
- 通讯作者:Golding NL
Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive.
内侧上橄榄双耳符合检测器神经元体树突 EPSP 的振幅标准化。
- DOI:10.1523/jneurosci.3110-16.2017
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Winters,BradleyD;Jin,Shan-Xue;Ledford,KennethR;Golding,NaceL
- 通讯作者:Golding,NaceL
Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.
- DOI:10.1523/jneurosci.2385-09.2010
- 发表时间:2010-02-10
- 期刊:
- 影响因子:0
- 作者:Scott LL;Mathews PJ;Golding NL
- 通讯作者:Golding NL
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Nace L Golding的其他文献
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{{ truncateString('Nace L Golding', 18)}}的其他基金
Single-cell computation in auditory brainstem and its impact on cortical coding and behavior
听觉脑干中的单细胞计算及其对皮质编码和行为的影响
- 批准号:
10455326 - 财政年份:2020
- 资助金额:
$ 43.03万 - 项目类别:
Single-Cell Computation in Auditory Brainstem and its Impact on Cortical Coding and Behavior
听觉脑干中的单细胞计算及其对皮质编码和行为的影响
- 批准号:
10795699 - 财政年份:2020
- 资助金额:
$ 43.03万 - 项目类别:
Discovery of functional cell types in the inferior colliculus with combined molecular-genetic and electrophysiological approaches
结合分子遗传学和电生理学方法发现下丘功能细胞类型
- 批准号:
9300564 - 财政年份:2017
- 资助金额:
$ 43.03万 - 项目类别:
Synergistic in vivo and in vitro approaches in the MSO
MSO 中的体内和体外协同方法
- 批准号:
8032251 - 财政年份:2011
- 资助金额:
$ 43.03万 - 项目类别:
Synergistic in vivo and in vitro approaches in the MSO
MSO 中的体内和体外协同方法
- 批准号:
8212018 - 财政年份:2011
- 资助金额:
$ 43.03万 - 项目类别:
Pre-Doctoral Training in Interdisciplinary Neuroscience
跨学科神经科学博士前培训
- 批准号:
10163823 - 财政年份:2004
- 资助金额:
$ 43.03万 - 项目类别:
PRE-DOCTORAL TRAINING IN INTERDISCIPLINARY NEUROSCIENCE
跨学科神经科学博士前培训
- 批准号:
10606255 - 财政年份:2004
- 资助金额:
$ 43.03万 - 项目类别:
Dendritic integration and synaptic plasticity in the MSO
MSO 中的树突整合和突触可塑性
- 批准号:
8516491 - 财政年份:2004
- 资助金额:
$ 43.03万 - 项目类别:
Dendritic integration and synaptic plasticity in the MSO
MSO 中的树突整合和突触可塑性
- 批准号:
8387949 - 财政年份:2004
- 资助金额:
$ 43.03万 - 项目类别:
Dendritic integration and synaptic plasticity in the MSO
MSO 中的树突整合和突触可塑性
- 批准号:
6809411 - 财政年份:2004
- 资助金额:
$ 43.03万 - 项目类别:
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