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.

上级丘（SC）在整合视觉和听觉输入以评估 突出重点，促进行动。然而，用于编码多模态的基础细胞类型和电路系统 在发育过程中用于形成电路的信息和机制在很大程度上仍然未知。 最近在老鼠遗传学方面的新技术的爆炸性发展使得神经元和电路可以被操纵 和特定的基因被删除，但令人惊讶的是，小鼠尚未被证明是一个模型， 学习感觉统合本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一个特定的时间内变化。 基因工程小鼠品系，以测试关于这些特性如何发展的假设。中央 待检验假设是视觉和听觉信息在小鼠SC中会聚以产生 多模态神经元形成多模态空间图，并使用视觉图映射对齐形式 模板匹配机制 具体目标1的目标是识别和确定小鼠SC的反应特性 视觉/听觉多模态神经元。为了实现这一点，清醒的，头部固定的小鼠，允许在一个 将用空间/时间/频谱受限的视觉和听觉刺激刺激，而 SC神经元的反应特性被记录使用高密度硅探针。SC神经 使用高密度硅，将同时记录每只小鼠中约170个神经元的活动 probes.数据分析将确定视觉、听觉和听觉的时空感受野， 视觉/听觉多模态神经元，它们的感觉整合特性，以及空间/时间/频谱 刺激因素的组成部分需要引发整合。创新包括使用虚拟听觉空间 提供局部声音的刺激，以及使用的记录和数据分析方法。 在具体目标2中提出的实验将测试长期存在的假设，即对齐和 使用视觉地图作为模板，以SC形式整合视觉和听觉输入。的 方法将是记录和分析听觉和视觉反应特性，如目标1所述，但从 转基因小鼠在SC中具有重复的视觉地图，并确定听觉地图是否 重新排列以与复制的可视地图对齐和集成。 拟议的研究是重要的，因为它将提供第一个全面的分析，接受 场特性的视觉/听觉整合神经元在小鼠SC，并将决定一般 这些属性是如何发展的。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潜在电路，特定的细胞类型 参与，以及动物的状态如何调节这些特性。