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

项目概要/摘要 主动聆听是听觉认知的核心，支持关键功能，例如流分离、 语言分析和感知学习。为此，大脑必须准确地代表物理 声学信号的属性，并随后根据其行为相关性解析声音。鉴于 主要特征（例如幅度和频谱内容）的编码通常始于专门的 脑干和中脑回路，声音获得行为相关性的机制很差 明白了。一个长期存在的假设是，听觉皮层的下降投射，与听觉皮层接触 大多数早期的上行听觉回路在将行为与声音相关性方面发挥着关键作用。确实， 下降的听觉皮层投射可以为“自上而下”的信号控制提供解剖学基础 声学特征的“自下而上”编码。尽管被认为很重要，但人们对它知之甚少 听觉皮层下降神经元在专心聆听中的功能，我们也不了解生物物理学 决定它们对中枢听觉处理的贡献的机制。我们的目标是解决这些问题 通过研究从听觉皮层到下听觉皮层的下降通路来了解行为小鼠的知识差距 丘，一个听觉中脑区域，对于感知复杂的声音至关重要。我们未发表的结果支持 听觉皮层神经元编码学习信息的工作假设，从而 传输信号，放大早期听觉中行为相关声音特征的表征 电路。我们的数据进一步表明听觉皮质丘脑活动的关键机制 主动聆听过程中的神经元是树突尖峰的非线性生成，这是一种强大的电事件， 在皮质神经元的顶端树突中启动，并驱动体细胞的高频突发放电。我们建议 使用亚细胞 2 光子 Ca2 成像、光遗传学和 对清醒、头部固定的小鼠进行行为测定。积极的结果将是建立功能性和 专心聆听期间听觉皮层下降通路运作的机械答案， 从而揭示了中枢听觉系统的一个关键但人们知之甚少的方面。

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 Our unpublished results support a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby transmitting signals that amplify the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.