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.

上级丘（SC）在处理听觉信息以评估显著性方面起着重要作用 并促进行动;然而，用于编码声源位置的基本细胞类型和电路 但基本上仍不为人所知。在灵长类动物和雪貂身上所做的工作表明， 深SC（dSC）中的神经元被组织在听觉空间的二维图中。最近， 在小鼠中也是如此，小鼠是一种已经拥有分子和遗传工具的生物体， 将使我们能够解剖电路来理解这个地图是如何形成的。 本申请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层输入 影响这些属性。我们的中心假设是，耳间水平差异（ILD）和 使用两组频谱线索来计算声音空间的二维映射;这些从 不同的脑干区域，并由皮质调节。具体目标1的目标是测试 假设声音空间的2维映射由SC使用ILD的组合进行编码， 两组光谱提示模式为了实现这一点，我们将刺激清醒的头部固定的小鼠，允许自由地 在跑步机上跑步，使用空间/时间/频谱受限的听觉刺激，然后同时记录SC 成千上万的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中的位置， 它们的RF对ILD和特定频率组合的依赖性，以及这些特性是否 由运动调节。具体目标2中提出的实验将检验SC 通过组合来自不同脑干核团的输入来计算声音位置。我们会记录下 下丘臂、IC外核和外侧核的性质 丘系的听觉刺激，并比较其RF性能的SC。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， 他们对SC响应的具体贡献。在具体目标3中，我们检验了直接 从听觉皮层到SC的投射用于通过以下方式调节dSC神经元的响应特性： 在缺乏皮质-丘投射的小鼠中测量听觉SC神经元的反应特性， 以及那些通过光遗传学使他们的听觉皮质-丘投射沉默的人。 该研究计划具有重要意义，因为其结果将建立小鼠SC作为研究模型 听觉空间映射和最终的听觉/视觉空间整合。我们的研究结果也将导致更好的 理解用于计算清醒行为动物的听觉场景的神经元回路，以及 将有助于发现听觉系统缺陷的神经发育障碍。