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

项目摘要/摘要 主动倾听是听觉认知的核心，支持流分离等关键功能， 语言分析和知觉学习。为此，大脑必须准确地代表身体 声音信号的属性，并随后基于它们的行为相关性来解析声音。鉴于 对主要特征(如幅度和光谱内容)的编码通常从专门的 脑干和中脑回路，声音获得行为关联的机制很差 明白了。一个长期存在的假设是，来自听觉皮质的下行投射 大多数早期提升的听觉回路，在将行为关联归因于声音方面起着关键作用。的确， 下降的听觉皮质投射可以为“自上而下”的信号提供控制的解剖学基础 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 听觉皮质神经元下行在注意听中的作用，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 通过研究从听觉皮质到下层的下行通路研究行为小鼠的知识差距 丘脑，一个听觉中脑区域，对感知复杂的声音至关重要。我们未公布的结果支持 一种工作假说，通过该假说，听觉皮质-丘脑神经元编码学习信息，从而 在早期听觉中传递放大行为相关声音特征表征的信号 电路。我们的数据进一步表明，听觉皮质-丘脑活动的一个关键机制 主动听音过程中的神经元是树突棘波的非线性产生，强大的电事件 在皮质神经元的顶端树突中启动，并在胞体驱动高频爆发式放电。我们建议 使用亚细胞双光子钙成像、光遗传学和 清醒的头部固定小鼠的行为分析。积极的结果将是建立功能性和 在专心聆听期间，对下行听觉皮质通路的操作的机械回答， 从而揭示了中枢听觉系统中一个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 Our unpublished results support a working hypothesis whereby auditory cortico-collicular neurons encode learned information, thereby transmitting signals that amplify the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.