Extratelencephalic contributions to auditory categorization

端脑外对听觉分类的贡献

• 批准号: 10915110
• 负责人: Ross Stewart Williamson
• 金额: $ 6.49万
• 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/10915110
• 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 听觉引导行为在日常生活中是普遍存在的，每当听觉信息被用来引导 我们做出的决定和我们采取的行动。其中一种行为是听觉分类，这是一个反映 将自下而上的感官刺激转化为离散的感知类别并使用这些感知类别的能力 分类以驱动后续操作。虽然这一过程在行为和 认知水平，令人惊讶的是，很少有人知道的外显神经回路机制，基础分类 计算以及这种计算的结果如何驱动行为结果。 我们认为，听觉信息转化为适当的行为反应是必要的， 全脑的奋进听觉皮层的深层产生了几个巨大的投射系统 对许多下游大脑区域产生影响。其中，层内的端脑外（ET）神经元 5b一直被认为是典型的“广播”神经元，汇集来自各种来源的输入， 在大脑中传递信号这些神经元的独特之处在于它们提供了唯一的直接 新皮层和各种行为相关的皮层下结构之间的联系，将它们置于一个 他们处于特权地位，可以很容易地影响听觉引导的行为。 为了了解ET神经元在神经行为中的作用，需要在体内，细胞类型特异性地 记录，在清醒的行为动物。为此，我们设计了一个新颖的听觉分类任务， 可以很容易地被头部固定的老鼠学会。我们的初步数据，包括解剖学和生理学数据， ET神经元在学习过程中对离散的感知类别具有选择性，这种选择性是通过介导的。 由高阶皮层自上而下的输入所控制。该提案的目标是利用尖端技术， 测试三个具体的假设：（1）ET神经元是必要的听觉分类，这种必要性是 学习依赖性和特异性轴突侧支（Aim 1），（2）ET反应特性改变 通过学习来反映离散的感知类别（目标2），以及（3）ET学习的类别选择性是 通过来自高阶皮层的自上而下的输入来塑造，高阶皮层充当灵活的、任务相关的过滤器（Aim 3）。 结合起来，这项研究将朝着理解下行回路的作用迈出重要的第一步。 将揭开更大的听觉通路，超越其经典的终点， 初级听觉皮层