Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
基本信息
- 批准号:8968241
- 负责人:
- 金额:$ 32.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-12-01 至 2017-11-30
- 项目状态:已结题
- 来源:
- 关键词:AMPA ReceptorsAction PotentialsAdultAffectAgeAnimalsAuditoryBrainBrain StemBuffersCell NucleusCellsComputer SimulationCouplingDataDendritesDockingEgtazic AcidElectrophysiology (science)EventExcitatory Postsynaptic PotentialsExhibitsExocytosisFiberFire - disastersFrequenciesFutureGlutamatesHealthHearingHearing problemImageryImaging TechniquesIndiumLeadLengthMeasuresMedialMembraneMusNerveNeuronsOutputPhosphorus 32PhysiologicalPlayProceduresPropertyResearchResolutionRodentRoleRyanodineSignal TransductionSliceSound LocalizationSourceSpeedStagingStimulusStructure-Activity RelationshipSynapsesTechniquesTemperatureTestingTimeTrainingVesicleWeaningWorkaging populationauditory pathwaychannel blockershearing impairmentimprovedinsightjuvenile animalmature animalmouse developmentmyelinationneuronal cell bodyneurotransmitter releasenovelpatch clamppostnatalpostsynapticpresynapticpreventranpirnasesoundsynaptic depressiontransmission processtrapezoid bodytreatment strategy
项目摘要
DESCRIPTION (provided by applicant): The large calyx of Held nerve terminal is a pivotal element in the circuitry that computes sound source localization in the mammalian auditory brainstem. Precise timing of action potential output from this synapse is thought to be central for
this task. However, the synaptic mechanisms that modulate and preserve action potential timing during high frequency firing are not well understood in mature animals because of the difficultly of recording and visualizing neurons in the heavily myelinated adult brainstem. Our lab has pioneered patch clamp recordings in brainstem slices from more mature and adult-like stages of mouse development, when they fully acquire their fine-tuned ability to hear and localize sound. The first hypothesis to be tested is that the large amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) observed in mature calyx of Held synapses is due to a highly synchronous form of multiquantal release. We suggest that these large and multiquantal mEPSCs are a natural consequence of the progressively tighter coupling of Ca2+ channels to docked vesicles as the synapse matures. We will reconstruct the active zones of mature calyces at a resolution of 3-5 nm and correlate this information with our quantal analysis at the single vesicle exocytosis level. Novel insights into the structure and function relationship of auditory synapses will thus be revealed. The second hypothesis to be tested is that a fast Ca2+-dependent recruitment of vesicles from a reserve pool, triggered by the opening of presynaptic Ca2+ stores, produces a transient EPSC enhancement, or a late-tetanic rebound, during a stimulus train in more mature synapses. We will test this hypothesis by using pharmacological approaches that either block increases in Ca2+ concentration or block the Ca2+ stores from releasing Ca2+. The third hypothesis to be tested is that postsynaptic MNTB principal cell dendrites play a major role in shortening the excitatory postsynaptic potential (EPSP) decay. We hypothesize that this "dendritic speeding" of the evoked EPSP enhances the precision of postsynaptic spikes triggered by afferent fiber stimulation at high frequencies. Finally, to study the passive and active properties of the adult-like MNTB principal cells and their dendrites we will use patch-clamp and Ca2+ imaging techniques. This will allow us to build realistic computer models of how the MNTB cell integrates synaptic inputs and fires action potentials to preserve the timing of incoming sound signals.
描述(由申请人提供):Held神经末梢的大萼是计算哺乳动物听觉脑干中声源定位的电路中的关键元件。从这个突触输出动作电位的精确时间被认为是神经元活动的中心。
这个任务。然而,在高频率放电过程中调节和保持动作电位计时的突触机制在成熟动物中还没有得到很好的理解,因为在有大量髓鞘的成年脑干中难以记录和可视化神经元。我们的实验室率先在小鼠发育的更成熟和类似成年阶段的脑干切片中进行膜片钳记录,当它们完全获得听到和定位声音的微调能力时。要测试的第一个假设是,自发的小型兴奋性突触后电流(mEPSC)的大幅度观察到的成熟的萼举行突触是由于一个高度同步的形式的多量子释放。我们认为,这些大的和多量子mEPSCs是一个自然的结果,逐步紧密耦合的钙通道停靠囊泡作为突触成熟。我们将在3-5 nm的分辨率下重建成熟肾盏的活性区,并将此信息与我们在单个囊泡胞吐水平上的量子分析相关联。从而揭示听觉突触的结构和功能关系的新见解。待检验的第二个假设是,突触前Ca 2+商店的开放触发的储备池中的囊泡的快速Ca 2+依赖性募集,在更成熟的突触中的刺激序列期间产生短暂的EPSC增强或迟发强直性反弹。我们将通过使用药理学方法来测试这一假设,该方法可以阻止Ca 2+浓度的增加或阻止Ca 2+储存释放Ca 2+。要测试的第三个假设是,突触后MNTB主细胞树突在缩短兴奋性突触后电位(EPSP)衰减中发挥了重要作用。我们推测,这种“树突加速”的诱发EPSP增强的精度突触后锋电位所触发的传入纤维刺激在高频率。最后,我们将利用膜片钳技术和钙离子成像技术研究成年样MNTB主细胞及其树突的被动和主动特性。这将使我们能够建立逼真的计算机模型,了解MNTB细胞如何整合突触输入并激发动作电位,以保持传入声音信号的时间。
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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HENRIQUE Prado VON GERSDORFF其他文献
HENRIQUE Prado VON GERSDORFF的其他文献
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{{ truncateString('HENRIQUE Prado VON GERSDORFF', 18)}}的其他基金
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
10672937 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
10471772 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
10510150 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
8575315 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
8432349 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Modulation of Exocytosis and Excitability in Mature Auditory Brainstem Neurons
成熟听觉脑干神经元胞吐作用和兴奋性的调节
- 批准号:
9974250 - 财政年份:2012
- 资助金额:
$ 32.56万 - 项目类别:
Dynamic modulation of retinal ribbon-type synapses
视网膜带状突触的动态调制
- 批准号:
7383768 - 财政年份:2002
- 资助金额:
$ 32.56万 - 项目类别:
Dynamic Modulation of Retinal Ribbon-Type Synapses
视网膜带状突触的动态调制
- 批准号:
7057232 - 财政年份:2002
- 资助金额:
$ 32.56万 - 项目类别:
Dynamic modulation of retinal ribbon-type synapses
视网膜带状突触的动态调制
- 批准号:
8632259 - 财政年份:2002
- 资助金额:
$ 32.56万 - 项目类别:
Dynamic Modulation of Retinal Ribbon-Type Synapses
视网膜带状突触的动态调制
- 批准号:
6751897 - 财政年份:2002
- 资助金额:
$ 32.56万 - 项目类别:
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