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)在处理听觉信息以评估显著程度方面起着重要作用 并促进行动；然而，用于编码声源位置的底层单元类型和电路 在很大程度上仍然不为人知。在灵长类动物和雪貂身上所做的研究表明， 深部SC(DSC)中的神经元被组织在听觉空间的二维地图中。这是最近发生的 在小鼠身上也是如此，这种有机体已经拥有了可用的分子和遗传工具 将使我们能够剖析电路以了解这张图是如何形成的。 这项应用的总体目标是确定听觉神经元的功能特性。 鼠标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，耳间水平差(ILD)和 两组光谱线索用于计算声音空间的二维图；它们继承自 不同的脑干区域，并由大脑皮层调节。具体目标1的目标是测试 假设声音空间的二维映射由SC使用ILD和 两套光谱线索模式。为了实现这一点，我们将刺激清醒的头部固定的小鼠，允许自由 在跑步机上跑步，在空间/时间/频谱受限的听觉刺激下，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ILDS和特定频率组合的依赖，以及如果这些属性 由运动调节的。在特定目标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团的输入来计算声音位置。我们将记录下回复 下丘臂部、下丘外核和外侧核的性质 Lemniscus对听觉刺激的影响，并将其射频特性与SC中的进行比较。我们还将使用 光遗传学：选择性地兴奋或抑制从这些区域投射到SC的神经元，以便识别 他们对SC反应的具体贡献。在特定的目标3中，我们检验了这样的假设 从听觉皮质到SC的投射被用来调节DSC神经元的反应特性 在缺乏皮质-丘脑投射的小鼠中，测量听觉SC神经元的反应特性， 而在那些通过光遗传学使其听觉皮质-丘脑投射消失的人中。 提出的研究计划具有重要意义，因为研究结果将建立小鼠SC作为研究的模型 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 了解用于计算清醒行为动物的听觉场景的神经元电路，以及 将照亮在听觉系统中有缺陷的神经发育障碍。