Multisensory integration in the mouse superior colliculus

小鼠上丘的多感觉整合

• 批准号: 10308501
• 负责人: DAVID A FELDHEIM
• 金额: $ 18.67万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10308501
• 关键词: Animals; Area; Auditory; Barn Owls; Brain; Brain Stem; Complex; Data Analyses; Defect; Development; EPHA3 gene; Engineering; Exhibits; Explosion; Felis catus; Ferrets; Future; Genes; Genetic; Genetic Engineering; Genetically Engineered Mouse; Goals; Head; Hearing; Individual; Knock-in Mouse; Knowledge; Maps; Methods; Midbrain structure; Modality; Modeling; Mus; Nature; Neurodevelopmental Disorder; Neurons; Outcome; Patients; Pattern; Perception; Play; Primates; Process; Property; Public Health; Research; Retinal Ganglion Cells; Role; Running; Schizophrenia; Sensory; Sensory Disorders; Silicon; Sound Localization; Stimulus; Structure; Study models; Symptoms; Testing; Time; Transgenic Mice; Vision; Visual; Work; anatomical tracing; auditory nuclei; auditory stimulus; autism spectrum disorder; awake; axon guidance; base; cell type; density; experience; experimental study; individuals with autism spectrum disorder; innovation; mouse genetics; mouse model; multimodality; multisensory; neuropsychiatric disorder; new technology; receptive field; relating to nervous system; response; sensory input; sensory integration; spatiotemporal; superior colliculus Corpora quadrigemina; treadmill; virtual; visual map; visual receptive field; visual stimulus

The superior colliculus (SC) plays a critical role in integrating visual and auditory inputs to assess saliency and promote action. However, the underlying cell types and circuitry used to encode multimodal information and the mechanisms used during development to form the circuitry remain largely unknown. The recent explosion of new technology in mouse genetics allows neurons and circuits to be manipulated and specific genes to be removed, but surprisingly, the mouse has not yet been shown to be a model to study sensory integration. The overall objective of this proposal is to determine the functional properties of visual/auditory multisensory neurons in the mouse SC, to determine how these properties change in a mouse line genetically engineered to test hypotheses about how these properties develop. The central hypothesis to be tested is that visual and auditory information converge in the mouse SC to create multimodal neurons that form a multimodal map of space, and that map alignment forms using a visual map template-matching mechanism. The goal of Specific Aim 1 is to identify, and determine the response properties of, mouse SC visual/auditory multimodal neurons. To accomplish this, awake, head-fixed mice, allowed to freely run on a treadmill, will be stimulated with spatially/temporally/spectrally restricted visual and auditory stimuli while the SC neuronal response properties are being recorded using high-density silicon probes. The SC neural activity of ~170 neurons will be simultaneously recorded from in each mouse, using high-density silicon probes. Data analysis will determine the spatiotemporal receptive fields of the visual, auditory and visual/auditory multimodal neurons, their sensory integration properties, and the spatial/temporal/spectral components of the stimulus needed to elicit integration. Innovations include the use of virtual auditory space stimuli to present localized sound, and the recording and data analysis methods used. Experiments proposed in Specific Aim 2 will test the longstanding hypothesis that the alignment and integration of the visual and auditory inputs in the SC form using the visual map as a template. The approach will be to record and analyze the auditory and visual response properties as in Aim 1 but from transgenic mice engineered to have a duplicated visual map in the SC, and determine if the auditory map rearranges to align and integrate with the duplicated visual map. The proposed research is significant because it will provide the first comprehensive analysis of the receptive field properties of visual/auditory integrative neurons in the mouse SC, and will determine the general principles of how these properties develop. The results of this work can be exploited immediately and in the future, to determine the underlying circuitry used to integrate sensory information, the specific cell types involved, and how the state of the animal modulates these properties.

上丘（SC）（SC）在整合视觉和听觉输入中起着至关重要的作用 显着性并促进行动。但是，用于编码多模式的基础细胞类型和电路 发育过程中使用的信息和机制在很大程度上未知。 老鼠遗传学中新技术的最新爆炸允许操纵神经元和电路 和要去除的特定基因，但令人惊讶的是，尚未证明小鼠是一个模型 研究感觉整合。该提案的总体目的是确定 鼠标SC中的视觉/听觉多感官神经元，以确定这些属性如何变化 小鼠线经过基因设计，以检验有关这些特性如何发展的假设。中央 要测试的假设是，视觉和听觉信息在鼠标SC中收敛以创建 多模式神经元形成多模式的空间图，并使用视觉映射形成图形对齐方式 模板匹配机制。 特定目标1的目标是识别和确定鼠标SC的响应属性 视觉/听觉多模式神经元。为了实现这一目标，醒着，固定的老鼠可以自由地在 跑步机将通过空间/时间/频谱受限的视觉和听觉刺激刺激 使用高密度硅探针记录SC神经元反应特性。 SC神经 使用高密度硅的活性〜170个神经元将同时从每只小鼠中记录 探针。数据分析将确定视觉，听觉和 视觉/听觉多模式神经元，其感觉积分属性和空间/时间/光谱 引起整合所需的刺激组成部分。创新包括使用虚拟听觉空间 刺激呈现局部声音，以及所使用的记录和数据分析方法。 特定目标2中提出的实验将检验以下长期假设 使用视觉映射作为模板以SC形式的视觉和听觉输入集成。这 方法是像AIM 1一样记录和分析听觉和视觉响应属性 经过设计的转基因小鼠在SC中具有重复的视觉图，并确定听觉地图是否是 重新安排以与重复的视觉图对齐并集成。 拟议的研究很重要，因为它将提供对接受性的首次综合分析 鼠标SC中视觉/听觉整合神经元的现场属性，并将确定一般 这些属性如何发展的原则。这项工作的结果可以立即利用 未来，为了确定用于整合感觉信息的基础电路，特定的单元格类型 涉及，以及动物状态如何调节这些特性。