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

下降听觉通路中行为相关活动的树突机制

基本信息

批准号：
10322647
负责人：
Pierre F Apostolides
金额：
$ 46.71万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10322647
关键词：
Acoustics Active Listening Address Anatomy Animals Apical Attention Auditory Auditory area Auditory system Behavioral Behavioral Assay Biophysical Process Brain Brain Stem Cognition Cognitive Complex Data Dendrites Detection Discrimination Epidemic Event Feedback Frequencies Generations Glutamates Goals Head Hearing Hearing problem Image In Vitro Inferior Colliculus Knowledge Learning Light Linguistics Link Mediating Midbrain structure Mus Neurons Noise-Induced Hearing Loss Outcome Output Pathway interactions Perception Perceptual learning Play Presbycusis Public Health Quality of life Rewards Role Sensory Signal Transduction Stimulus Stream Synapses Testing Time Tinnitus Work auditory discrimination auditory pathway auditory processing awake base experience experimental study hearing impairment improved neuronal cell body novel strategies operation optogenetics physical property prevent segregation sensory system sound two-photon

项目摘要

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.

项目摘要/摘要主动聆听是听觉认知的核心，支持关键功能，例如流隔离，语言分析和感知学习。为此，大脑必须准确代表物理声学信号的属性和随后根据其行为相关性解析声音。然而主要特征的编码（例如振幅和光谱含量）通常以专业为开始脑干和中脑电路，声音达到行为相关性的机制很差理解。一个长期的假设是，从听觉皮层降临的预测，接触大多数早期上升的听觉电路，在将行为相关性赋予声音中起着至关重要的作用。的确，下降的听觉皮质预测可以为“自上而下”信号提供解剖基板声学特征的“自下而上”编码。尽管认为这很重要，但对在专注的聆听中降序的听觉皮质神经元的功能，我们也不了解生物物理决定其对中央听觉处理的贡献的机制。我们的目标是解决这些通过研究从听觉皮层到劣等的降序途径，在行为小鼠中的知识差距 Colliculus是一个听觉中脑区域，对于感知复杂声音至关重要。我们未发表的结果支持听觉皮层 - 典型神经元编码学习的信息的工作假设，从而传输信号在早期听觉中放大行为相关的声音功能的表示电路。我们的数据进一步表明，听觉皮层 - 典型活动的关键机制主动聆听过程中的神经元是非线性的树突尖峰，强大的电气事件在皮质神经元的顶端树突中启动，并在躯体上驱动高频爆发。我们建议使用亚细胞2光子Ca2+成像，光遗传学和醒着，头部固定的小鼠的行为测定。积极的结果将是建立功能和在细心聆听期间运行的机械答案，从而使中央听觉系统的一个关键但鲜为人知的方面散发出灯光。