Function and regulation of action potential bursts in the auditory system.

听觉系统动作电位爆发的功能和调节。

• 批准号: 8675336
• 负责人: Kevin J Bender
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8675336
• 关键词: Action Potentials; Affect; Auditory; Auditory system; Axon; Back; Brain Stem; Brain region; Calcium Channel; Cells; Coupled; Cues; Data; Dendrites; Dopamine; Efferent Neurons; Electrophysiology (science); Ensure; Epilepsy; Failure; Fire - disasters; Frequencies; Functional disorder; Fusiform Cell; Generations; Goals; Image; Imaging Techniques; Learning; Mediating; Membrane; Mentors; Neurons; Noise; Optics; Output; Pathway interactions; Pharmacology; Phase; Phosphorylation; Photons; Play; Process; Regulation; Role; Second Messenger Systems; Shapes; Signal Pathway; Signal Transduction; Site; Sound Localization; Structure; Synapses; Synaptic plasticity; Techniques; Testing; Time; Tinnitus; Whole-Cell Recordings; Work; dorsal cochlear nucleus; multisensory; nerve supply; neuronal excitability; novel; postsynaptic; presynaptic; second messenger; sensor; sound; voltage

Project summary: Circuits in the auditory brainstem dorsal cochlear nucleus (DCN) are believed to aid in sound localization in the vertical plane using monaural cues. Moreover, DCN circuitry integrates auditory and non-auditory inputs to aid in orientation toward sounds or to suppress self-generated noise, thereby increasing the salience of external sounds. Our long-term goal is to understand the synaptic mechanisms that contribute to these functions. Multisensory integration is controlled, in part, by high-frequency action potential bursts from inhibitory cartwheel cells; yet the way in which bursts are generated, and the effects of burst inhibition on postsynaptic integration, remain unclear. The objective of this proposal is to define mechanisms governing burst generation, focusing on the role of newly-discovered low-threshold activated calcium channels localized to the site of action potential initiation in the axon initial segment. First, we will use a combination of electrophysiology and 2-photon imaging to identify signaling pathways that control neuronal output by regulating initial segment calcium channel activity. Second, we will take advantage of novel voltage imaging techniques to determine how calcium channels contribute to the generation of bursts in the initial segment. Finally, we will determine how inhibitory synaptic input affects integration in the efferent neurons of the DCN, fusiform cells, contrasting the effects of single action potentials and bursts.

项目摘要：听觉脑干背侧耳蜗核 (DCN) 中的电路被认为有助于 使用单声道线索在垂直平面上进行声音定位。此外，DCN 电路集成了听觉和 非听觉输入有助于定向声音或抑制自身产生的噪音，从而增加 外部声音的显着性。我们的长期目标是了解有助于突触的机制 到这些功能。多感觉统合在一定程度上是由高频动作电位爆发控制的 抑制性侧手翻细胞；然而爆发的产生方式以及爆发抑制的影响 突触后整合仍不清楚。该提案的目标是定义管理机制 爆发式生成，重点关注新发现的低阈值激活局部钙通道的作用 到轴突起始段的动作电位起始位点。首先，我们将使用组合 电生理学和 2 光子成像来识别控制神经元输出的信号通路 调节起始段钙通道活性。其次，我们将利用新颖的电压成像技术 确定钙通道如何促进初始片段中爆发的产生的技术。 最后，我们将确定抑制性突触输入如何影响 DCN 传出神经元的整合， 梭形细胞，对比单个动作电位和爆发的效果。