Coding of auditory space in the mouse superior colliculus

小鼠上丘听觉空间的编码

• 批准号: 10576405
• 负责人: DAVID A FELDHEIM
• 金额: $ 42.67万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576405
• 关键词: Animals; Area; Auditory; Auditory area; Auditory system; Brain; Brain Stem; Cell Nucleus; Code; Communication; Complex; Cues; Data Analyses; Dependence; Disease; Ear; Ferrets; Frequencies; Genetic; Goals; Head; Hearing; Human; Inferior Colliculus; Inherited; Knowledge; Lateral lemniscus; Light; Location; Locomotion; Mammals; Maps; Measures; Midbrain structure; Modeling; Modification; Molecular; Mus; Nature; Neurodevelopmental Disorder; Neurons; Organism; Pattern; Perception; Play; Population; Primates; Process; Property; Public Health; Research; Role; Running; Scheme; Shapes; Silicon; Sound Localization; Source; Testing; Visuospatial; Work; auditory processing; auditory stimulus; awake; cell type; experimental study; large datasets; neural; neuronal circuitry; optogenetics; receptive field; response; sound; spatial integration; spatiotemporal; superior colliculus Corpora quadrigemina; tool; treadmill; two-dimensional; visual map

The Superior Colliculus (SC) plays an essential role in processing auditory information to assess saliency and promote action; however, the underlying cell types and circuitry used to encode sound source locations remain largely unknown. Work done in primates and ferrets has shown that the receptive fields (RFs) of neurons in the deep SC (dSC) are organized in a 2-dimensional map of auditory space. This has recently been shown to also be true in the mouse, an organism that already has molecular and genetic tools available that will allow us to dissect circuitry to understand how this map forms. The overall objective of this application is to determine the functional properties of auditory neurons in the mouse SC, determine how these properties are encoded, and determine which brainstem and cortical inputs influence these properties. Our central hypothesis is that a combination of interaural level differences (ILD) and two sets of spectral cues are used to compute a 2-dimensional map of sound space; these are inherited from different brainstem regions and are modulated by the cortex. The goal of Specific Aim 1 is to test the hypothesis that the 2-dimensional map of sound space is encoded by the SC using a combination of ILDs and two sets of spectral cue patterns. To achieve this we will stimulate awake head-fixed mice, allowed to freely run on a treadmill, with spatially/temporally/spectrally restricted auditory stimuli, then simultaneously record SC neuronal response properties of thousands of auditory responsive neurons. Data analysis will determine the spatiotemporal and spectral/temporal receptive fields (RFs) of auditory neurons, their locations within the SC, the dependence of their RFs on ILDs and specific frequency combinations, and if these properties are modulated by locomotion. Experiments proposed in Specific Aim 2 will test the hypothesis that the SC computes sound location by combining inputs from different brainstem nuclei. We will record the response properties of the brachium of the inferior colliculus, the external nucleus of the IC, and the nucleus of the lateral lemniscus to auditory stimuli, and compare their RF properties to those in the SC. We will also use optogenetics to selectively excite or inhibit neurons that project from these areas to the SC in order to identify their specific contributions to the SC responses. In Specific Aim 3 we test the hypothesis that the direct projection from the auditory cortex to the SC is used to modulate the response properties of dSC neurons by measuring the response properties of auditory SC neurons both in mice that lack a cortico-collicular projection, and in those that have their auditory cortico-collicular projection silenced via optogenetics. The proposed research plan is significant because the results will establish the mouse SC as a model to study auditory spatial mapping and eventually auditory/visual spatial integration. Our findings will also lead to a better understanding of the neuronal circuitry used to compute auditory scenes in the awake behaving animal, and will shine light on neurodevelopmental disorders that have deficits in the auditory system.

上丘 (SC) 在处理听觉信息以评估显着性方面发挥着重要作用 并促进行动；然而，用于编码声源位置的底层细胞类型和电路 仍然很大程度上不为人所知。在灵长类动物和雪貂身上所做的工作表明， 深层 SC (dSC) 中的神经元被组织成听觉空间的二维图。这是最近 在小鼠身上也证明了这一点，小鼠是一种已经拥有可用分子和遗传工具的生物体 将使我们能够剖析电路以了解该地图是如何形成的。 该应用程序的总体目标是确定听觉神经元的功能特性 小鼠 SC，确定这些属性是如何编码的，并确定哪些脑干和皮质输入 影响这些属性。我们的中心假设是，耳间电平差异 (ILD) 和 两组频谱线索用于计算声音空间的二维图；这些都是继承自 不同的脑干区域并受到皮质的调节。具体目标 1 的目标是测试 假设声音空间的二维图是由 SC 使用 ILD 和 两组光谱提示模式。为了实现这一目标，我们将刺激清醒的头部固定小鼠，让其自由活动 在跑步机上跑步，在空间/时间/频谱上限制听觉刺激，然后同时记录 SC 数千个听觉反应神经元的神经元反应特性。数据分析将确定 听觉神经元的时空和频谱/时间感受野（RF），它们在 SC 内的位置， 它们的 RF 对 ILD 和特定频率组合的依赖性，以及这些属性是否 由运动调制。具体目标 2 中提出的实验将检验 SC 的假设 通过组合来自不同脑干核团的输入来计算声音位置。我们将记录回复 下丘臂、IC 外核和外侧核的特性 丘系到听觉刺激，并将其射频特性与 SC 中的射频特性进行比较。我们还将使用 光遗传学选择性地激发或抑制从这些区域投射到 SC 的神经元，以便识别 他们对 SC 应对措施的具体贡献。在具体目标 3 中，我们检验了以下假设：直接 从听觉皮层到 SC 的投射用于通过以下方式调节 dSC 神经元的反应特性： 测量缺乏皮质-丘脑投射的小鼠的听觉 SC 神经元的反应特性， 以及那些通过光遗传学使听觉皮层投射沉默的人。 所提出的研究计划意义重大，因为该结果将建立小鼠 SC 作为研究模型 听觉空间映射以及最终的听觉/视觉空间整合。我们的发现也将带来更好的结果 了解用于计算清醒行为动物听觉场景的神经回路，以及 将揭示听觉系统缺陷的神经发育障碍。