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: 7952332
• 负责人: Kevin J Bender
• 金额: $ 9.72万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952332
• 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; public health relevance; second messenger; sensor; sound; voltage

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Dysfunctions in low-voltage activated calcium channel activity contributes to hyperexcitability in many brain regions, and may be etiological to tinnitus and epilepsy. This proposal examines the function and regulation of low-voltage activated calcium channels localized to the site of action potential initiation. Understanding how these channels affect neuronal output may uncover new avenues for treatment of hyperexcitability conditions.

描述（由申请人提供）：听觉脑干耳蜗背核（DCN）中的回路被认为有助于使用单耳线索在垂直平面中进行声音定位。此外，DCN电路集成了听觉和非听觉输入，以帮助对声音的定向或抑制自生噪声，从而增加外部声音的显著性。我们的长期目标是了解有助于这些功能的突触机制。多感觉整合的控制，在一定程度上，从抑制侧手翻细胞的高频动作电位爆发，但爆发产生的方式，以及爆发抑制对突触后整合的影响，仍然不清楚。本提案的目的是确定突发产生的机制，重点是新发现的低阈值激活的钙通道定位于轴突起始段的动作电位起始位点的作用。首先，我们将使用电生理学和双光子成像的组合来识别通过调节初始段钙通道活性来控制神经元输出的信号通路。其次，我们将利用新的电压成像技术，以确定如何钙通道有助于在初始段的爆发的产生。最后，我们将确定抑制性突触输入如何影响DCN，梭形细胞的传出神经元的整合，对比单一动作电位和爆发的影响。 公共卫生相关性：低电压激活的钙通道活动的功能障碍导致许多脑区域的过度兴奋，并且可能是耳鸣和癫痫的病因。本研究旨在探讨位于动作电位起始部位的低电压激活钙通道的功能和调节。了解这些通道如何影响神经元输出可能会发现新的途径治疗过度兴奋的条件。