Dendritic Mechanisms Underlying Behaviorally-Relevant Activity in a Descending Auditory Pathway

项目总结/摘要 主动倾听是听觉认知的核心，支持关键功能，如流分离， 语言分析和知觉学习。为此，大脑必须准确地再现物理 声学信号的特性，并随后基于它们的行为相关性来解析声音。而 诸如幅度和频谱内容之类的主要特征的编码通常开始于专门的 脑干和中脑回路，声音获得行为相关性的机制很差， 明白一个长期存在的假设是，听觉皮层的下行投射， 大多数早期的上行听觉回路在将行为相关性归因于声音方面起着关键作用。的确， 下行的听觉皮层投射可以为“自上而下”的信号提供解剖学基础， 声学特征的“自下而上”编码。尽管有这种假定的重要性，但人们对 下行听觉皮层神经元在注意听中的功能，我们也不了解生物物理学 这些机制决定了它们对中枢听觉处理的贡献。我们的目标是解决这些问题 通过研究从听觉皮层到下皮层的下行通路， 丘，一个对感知复杂声音至关重要的听觉中脑区域。我们未发表的结果支持 一个工作假设，即听觉皮质丘神经元编码学习信息，从而 传输信号，放大早期听觉中与行为相关的声音特征的表现， 电路.我们的数据进一步表明，一个关键的机制，潜在的活动，听觉皮质丘， 神经元在主动倾听过程中的一个重要特征是树突棘波的非线性生成， 起始于皮层神经元的顶端树突并驱动索马的高频爆发放电。我们提出 使用亚细胞双光子Ca 2+成像、光遗传学和 在清醒的、头部固定的小鼠中的行为测定。积极的结果将是建立功能和 在注意听的过程中，下行听觉皮层通路的运作的机械答案， 从而揭示了中枢听觉系统的关键但知之甚少的方面。

Project Summary/Abstract Active listening is central to auditory cognition, supporting critical functions such as stream segregation, linguistic analysis and perceptual learning. To this end, the brain must accurately represent the physical properties of acoustic signals and subsequently parse sounds based on their behavioral relevance. Whereas the encoding of primary features such as amplitude and spectral content typically begins in specialized brainstem and midbrain circuits, the mechanisms by which sounds attain behavioral relevance are poorly understood. A long-standing assumption is that descending projections from auditory cortex, which contact most early ascending auditory circuits, play a critical role in ascribing behavioral relevance to sounds. Indeed, descending auditory cortical projections could provide an anatomical substrate for "top-down" signals to control the "bottom-up" encoding of acoustic features. Despite this presumed importance, little is known about the function of descending auditory cortical neurons in attentive listening, nor do we understand the biophysical mechanisms that dictate their contribution to central auditory processing. Our goal is to address these knowledge gaps in behaving mice by studying the descending pathway from auditory cortex to inferior colliculus, an auditory midbrain region critical for perceiving complex sounds. Our unpublished results support a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby transmitting signals that amplify the representation of behaviorally relevant sound features in early auditory circuits. Our data further suggest that a key mechanism underlying the activity of auditory cortico-collicular neurons during active listening is the non-linear generation of dendritic spikes, powerful electrical events that initiate in the apical dendrites of cortical neurons and drive high-frequency burst firing at the soma. We propose testing these hypotheses using a unique combination of sub-cellular 2-photon Ca2+ imaging, optogenetics and behavioral assays in awake, head-fixed mice. The positive outcome will be to establish functional and mechanistic answers for the operation of a descending auditory cortical pathway during attentive listening, thereby shedding light on a critical yet poorly understood facet of the central auditory system.