Extratelencephalic contributions to auditory categorization

项目摘要 听觉引导行为在日常生活中无处不在，每当听觉信息被用来引导 我们所做的决定和所采取的行动。一种这样的行为是听觉分类，这是一个反映 将自下而上的感觉刺激转换为离散的感知类别并使用这些感知类别的能力 类别以驱动后续操作。尽管这一过程在行为和行为方面有很好的记录 在认知水平上，令人惊讶的是，人们对构成分类的显性神经回路机制知之甚少。 计算以及该计算的结果如何驱动行为结果。 我们认为，将听觉信息转化为适当的行为反应是必要的 一项全脑性的努力。听觉皮质的深层产生了几个巨大的投射系统 对大脑下游的许多区域产生影响。其中，层内的脑外(ET)神经元 5B长期以来一直被认为是典型的“广播”神经元，汇集了来自各种来源的输入和 在整个大脑中传递信号。这些神经元的独特之处在于它们提供了唯一直接的 新皮质和各种行为相关的皮质下结构之间的连接，将它们置于 他们可以很容易地影响听觉引导行为的特权地位。 要了解ET神经元在听觉引导行为中所起的作用，必须在体内、细胞类型特定的情况下 在清醒状态下的动物行为的录音。为此，我们设计了一种新颖的听觉分类任务 头部固定的小鼠可以很容易地学会。我们的初步数据，无论是解剖学还是生理学的，都认为 ET神经元在学习过程中对离散的知觉类别具有选择性，这种选择性是通过媒介实现的 通过来自高级皮质的自上而下输入。该提案的目标是利用尖端技术 检验三个具体的假设：(1)ET神经元是听觉分类所必需的，这一必要性是 学习依赖性和对不同轴突侧支的特异性(目标1)，(2)ET反应特性改变 通过学习来反映离散的知觉类别(目标2)和(3)ET学习的范畴选择性是 通过来自高级皮质的自上而下的输入形成，该输入充当灵活的、任务相关的过滤器(目标3)。 总而言之，这项研究将向理解下行回路的作用迈出重要的第一步 在听觉引导的行为中将揭开位于其经典终端之外的更大的听觉通路 初级听觉皮质。

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.