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) 在整合视觉和听觉输入以评估 突出并促进行动。然而，用于编码多模态的底层细胞类型和电路 开发过程中用于形成电路的信息和机制仍然很大程度上未知。 最近小鼠遗传学新技术的爆发使得神经元和电路可以被操纵 以及要去除的特定基因，但令人惊讶的是，小鼠尚未被证明是一种模型 研究感觉统合。该提案的总体目标是确定 小鼠 SC 中的视觉/听觉多感觉神经元，以确定这些特性如何在 小鼠品系经过基因工程改造，以测试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小鼠 SC 中汇聚以产生 多模态神经元形成多模态空间图，并使用视觉图来映射对齐形式 模板匹配机制。 具体目标 1 的目标是识别并确定小鼠 SC 的响应特性 视觉/听觉多模式神经元。为了实现这一目标，将清醒的、头部固定的小鼠允许在 跑步机，将受到空间/时间/光谱限制的视觉和听觉刺激的刺激，而 使用高密度硅探针记录 SC 神经元反应特性。 SC神经 使用高密度硅同时记录每只小鼠约 170 个神经元的活动 探针。数据分析将确定视觉、听觉和感知的时空感受野 视觉/听觉多模态神经元，它们的感觉统合特性，以及空间/时间/光谱 引发整合所需的刺激成分。创新包括使用虚拟听觉空间 呈现局部声音的刺激，以及所使用的记录和数据分析方法。 具体目标 2 中提出的实验将检验长期存在的假设，即对齐和 使用视觉图作为模板，将视觉和听觉输入整合到 SC 形式中。这 方法将是记录和分析听觉和视觉反应特性，如目标 1 所示，但从 转基因小鼠被设计成在 SC 中具有重复的视觉图，并确定听觉图是否 重新排列以与复制的视觉图对齐并集成。 所提出的研究意义重大，因为它将提供对接受性的首次全面分析。 小鼠 SC 中视觉/听觉整合神经元的场特性，并将决定一般 这些属性如何发展的原则。这项工作的成果可以立即被利用 未来，为了确定用于整合感觉信息的底层电路，特定的细胞类型 涉及，以及动物的状态如何调节这些特性。