Extratelencephalic contributions to auditory categorization

端脑外对听觉分类的贡献

• 批准号: 10641922
• 负责人: Ross Stewart Williamson
• 金额: $ 59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-10 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641922
• 关键词: Active Listening; Anatomy; Anesthesia procedures; Animal Behavior; Animals; Apical; Area; Auditory; Auditory area; Axon; Behavior; Behavioral; Brain; Brain region; Calcium; Categories; Cognitive; Corpus striatum structure; Data; Decision Making; Dendrites; Functional disorder; Genetic; Goals; Head; Image; Individual; Inherited; Knowledge; Learning; Life; Mediating; Midbrain structure; Monitor; Morphology; Motor; Mus; Neocortex; Neurons; Output; Parietal Lobe; Pathway interactions; Physiological; Pilot Projects; Play; Population; Positioning Attribute; Process; Property; Research; Role; Route; Sensory; Shapes; Signal Transduction; Source; Stimulus; Structure; System; Techniques; Testing; Viral; Work; association cortex; auditory categorization; auditory pathway; awake; behavioral outcome; behavioral response; cell type; design; flexibility; in vivo; insight; neocortical; neural; neural circuit; novel; optogenetics; response; sensory cortex; sensory stimulus; transmission process; two-photon

Project Summary Auditory-guided behavior is ubiquitous in everyday life, whenever auditory information is used to guide the decisions we make and the actions we take. One such behavior is auditory categorization, a process that reflects the ability to transform bottom-up sensory stimuli into discrete perceptual categories and use these perceptual categories to drive a subsequent action. Although this process is well-documented at the behavioral and cognitive levels, surprisingly little is known about the explicit neural circuit mechanisms that underlie categorical computation and how the result of this computation drives behavioral outcomes. We believe that the transformation of auditory information into an appropriate behavioral response is necessarily a brain-wide endeavor. The deep layers of the auditory cortex give rise to several massive projection systems that exert influence over many downstream brain areas. Of these, extratelencephalic (ET) neurons within layer 5b have long been regarded as canonical “broadcast” neurons, pooling inputs from a variety of sources and transmitting signals throughout the brain. These neurons are unique in that they provide the only direct connection between the neocortex and various behaviorally relevant subcortical structures, placing them in a privileged position where they can readily influence auditory-guided behavior. To understand the role that ET neurons play in auditory-guided behavior necessitates in vivo, cell-type specific recordings, in awake behaving animals. To this end, we have designed a novel auditory categorization task that can be readily learned by head-fixed mice. Our preliminary data, both anatomical and physiological, posits that ET neurons become selective to discrete perceptual categories across learning, and this selectivity is mediated by top-down input from higher-order cortex. The goal of this proposal is to leverage cutting-edge techniques to test three specific hypotheses: (1) ET neurons are necessary for auditory categorization, and this necessity is both learning-dependent and specific to distinct axon collaterals (Aim 1), (2) ET response properties change across learning to reflect discrete perceptual categories (Aim 2), and (3) ET learned categorical selectivity is shaped via top-down inputs from higher-order cortex that act as a flexible, task-dependent filter (Aim 3). Combined, this research will take an important first step towards understanding the role of descending circuits in auditory-guided behavior will unveil the greater auditory pathway that lies beyond its classical terminus in primary auditory cortex.

项目摘要 每天都有听觉引导的行为在日常生活中无处不在 我们做出的决定和采取的行动。一种这样的行为就是听觉类别，一个反映的过程 将自下而上的感觉刺激转化为离散感知类别并使用这些感知的能力 采取后续操作的类别。尽管此过程在行为和 认知水平，令人惊讶 计算以及该计算结果如何驱动行为结果。 我们认为，必须将听觉信息转化为适当的行为响应 一项大脑的努力。听觉皮层的深层产生了几个巨大的投影系统 这对许多下游大脑区域施加了影响。其中，层中的脑外脑（ET）神经元 长期以来，5B被认为是规范的“广播”神经元，从各种来源汇集了输入， 在整个大脑中传输信号。这些神经元是独特的，因为它们提供了唯一的直接 新皮层与各种行为相关的皮层结构之间的联系，将它们放在 特权位置可以容易影响听觉引导的行为。 了解ET神经元在体内必需的听觉引导行为中所起的作用，特定于细胞类型 录音，在醒着的动物中。为此，我们设计了一个新颖的听觉类别任务 可以通过固定的小鼠很容易学习。我们的初步数据（无论是解剖学还是物理数据）认为 ET神经元对整个学习的离散感知类别有选择性，并且这种选择性是介导的 通过高阶皮层的自上而下输入。该提议的目的是利用尖端技术 测试三个特定的假设：（1）ET神经元对于听觉类别是必需的，这是必要的 学习依赖性且特定于不同的轴突侧支（AIM 1），（2）ET响应特性发生了变化 在学习中反映离散的感知类别（AIM 2）和（3）ET学习的分类选择性是 通过高阶皮层的自上而下输入形状，可作为灵活的任务依赖性滤波器（AIM 3）。 合并后，这项研究将迈出重要的第一步，以理解下降电路的作用 在听觉引导的行为中，将揭示出更大的听觉途径，该途径超出了其经典末端 主要听觉皮层。