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

项目概述：听觉脑干耳蜗背核（DCN）中的回路被认为有助于 使用单声道线索在垂直平面中的声音定位。此外，DCN电路整合了听觉和 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 外部声音的突出性。我们的长期目标是了解突触机制， 这些功能。多感觉整合在某种程度上是由来自大脑皮层的高频动作电位爆发控制的。 抑制性侧手翻细胞;然而，爆发产生的方式，以及爆发抑制对 突触后整合，仍然不清楚。本提案的目的是确定管理 爆发的产生，重点是新发现的低阈值激活的钙通道的作用， 轴突起始段的动作电位起始点。首先，我们将结合使用 电生理学和双光子成像，以确定控制神经元输出的信号通路， 调节起始段钙通道活性。第二，我们将利用新颖的电压成像 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传出神经元的整合， 梭形细胞，对比单个动作电位和爆发的作用。

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.