Coding of auditory space in the mouse superior colliculus

小鼠上丘听觉空间的编码

• 批准号: 10361193
• 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/10361193
• 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; Goals; Head; Hearing; Inferior Colliculus; Inherited; Knowledge; Lateral lemniscus; Lead; Light; Location; Locomotion; Maps; Measures; Midbrain structure; Modeling; Modification; Molecular Genetics; 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; base; cell type; experimental study; human error; large datasets; neuronal circuitry; optogenetics; receptive field; relating to nervous system; 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）（SC）在处理听觉信息以评估显着性方面起着至关重要的作用 并促进行动；但是，用于编码声音源位置的基础单元格类型和电路 在很大程度上未知。在灵长类动物和雪貂中完成的工作表明，接受场（RFS） 深SC（DSC）中的神经元在听觉空间的二维图中组织。最近已经 显示在小鼠中也是如此，这是一种已经具有分子和遗传工具的生物 将使我们能够解剖电路以了解该地图的形成方式。 该应用的总体目的是确定听觉神经元在 鼠标SC，确定这些特性的编码方式，并确定哪些脑干和皮质输入 影响这些特性。我们的核心假设是，跨层间差异（ILD）和 两组光谱提示用于计算声音空间的二维图；这些是从 不同的脑干区域，由皮层调节。特定目标1的目的是测试 二维声音空间图的假设是由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，可以自由 在跑步机上运行，​​具有空间/时间/频谱限制的听觉刺激，然后同时记录SC 数千个听觉反应性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光谱/时间接受场（RFS），其位置在SC中， 其RF对ILD和特定频率组合的依赖性，以及这些属性是否为 通过运动调节。特定目标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的输入来计算声音位置。我们将记录响应 下丘的臂的特性，IC的外核和横向核的特性 Lemniscus与听觉刺激，并将其RF属性与SC中的RF属性进行比较。我们还将使用 光遗传学可选择性地激发或抑制从这些区域向SC投射的神经元，以识别 他们对SC响应的具体贡献。在特定目标3中，我们检验了直接的假设 从听觉皮层到SC的投影用于调节DSC神经元的响应特性 在缺乏皮质 - 典型投影的小鼠中测量听觉SC神经元的响应特性， 在那些通过光遗传学沉默的具有听觉皮质 - 胶体投影的人中。 提出的研究计划很重要，因为结果将建立鼠标SC作为研究模型 听觉空间映射，最终是听觉/视觉空间集成。我们的发现也将导致更好 了解用于计算醒着的动物中听觉场景的神经元电路， 将在听觉系统缺陷的神经发育障碍上发光。