Mechanisms of olfactory signal processing

嗅觉信号处理机制

• 批准号: 10604284
• 负责人: NATHAN Eric SCHOPPA
• 金额: $ 41.45万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604284
• 关键词: Animal Behavior; Animals; Association Learning; Behavior; Behavioral; Binding Proteins; Brain; Cells; Communication; Data; Development; Discrimination; Disease; Electric Stimulation; Electrophysiology (science); Equilibrium; Exhibits; FMR1; Female; Foundations; Fragile X Gene; Fragile X Syndrome; Frequencies; Functional disorder; Future; Gene Expression; Glutamate Decarboxylase; Goals; Human; Hypersensitivity; Impairment; Individual; Induced Mutation; Interneurons; Knockout Mice; Link; Mediating; Messenger RNA; Methods; Modality; Modeling; Morphologic artifacts; Mus; Mutation; Odors; Olfactory Pathways; Output; Performance; Protein Isoforms; Proteins; Recovery; Rodent; Role; Sensory; Slice; Smell Perception; Social Interaction; Structure; Synapses; System; Tamoxifen; Testing; Translations; X Chromosome; autism spectrum disorder; awake; behavioral impairment; cell type; cognitive ability; experimental study; fly; granule cell; in vivo; interdisciplinary approach; male; mitral cell; mouse model; neural; olfactory bulb; patch clamp; sensory system; signal processing; social communication

Project Summary/Abstract (ASDs) an Individuals communication, can spectrum disorders results from the loss of expression of the Fragile X mental retardation protein (FMRP), mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation. with FXS can exhibit a range of debilitating deficits in cognitive abilities, social interactions and and sensory processing. Deficits in sensory processing, often observed as hypersensitivity, contribute to other deficits associated with FXS (e.g., in social interactions). The Fragile X syndrome (FXS) is the single most common monogenetic cause of autism in humans. FXS broad objective of this proposal is to examine dysfunction in the olfactory system of mouse models for Fragile X with reduced expression of the mouse gene for FMRP, Fmr1. Surprisingly, despite the overwhelming importance of olfaction for rodents, there are few studies in this sensory modality in Fmr1 KO mice. Our goals, divided across three Aims, will be: Aim 1: To test the hypothesis that Fmr1 regulates inhibitory synaptic connections in the bulb. Aim 2: To test the hypothesis that Fmr1 regulates local network activity in the bulb by controlling inhibitory synaptic connections. Aim 3. To test the hypothesis that Fmr1 regulates olfactory behavior and bulbar oscillations in awake behaving mice by controlling inhibitory synaptic connections. Our studies will utilize a variety of approaches including patch-clamp recordings in brain slices, ultrastructural analyses, behavioral experiments, and in vivo electrophysiological recordings. Mouse models will include whole-animal Fmr1 KO mice, which is the most widely used mouse model of FXS, along with conditional KO and recovery mice in which Fmr1 expression is selectively and inducibly manipulated in GAD65-expressing GABAergic interneurons. This multidisciplinary approach will enable us to identify dysfunction in olfaction that results from altered Fmr1 expression at levels ranging from single synapses to whole-animal behavior and also link the changes observed at the different levels.

项目摘要/摘要 (自闭症) 一个 个人 沟通， 能 谱系障碍 由于脆性X智力低下蛋白(FMRP)的表达缺失， 编码在X染色体上的mRNA结合蛋白参与抑制蛋白质翻译。 患有FXS的人会在认知能力、社交和社交方面出现一系列令人衰弱的缺陷 和感官处理。感觉处理的缺陷，通常被观察到为高敏感症， 造成与FXS相关的其他缺陷(例如，在社交方面)。这个 脆性X综合征(FXS)是自闭症最常见的单基因致病因素 在人类身上。FXS 这项工作的广泛目标 建议检查脆性X染色体减少的小鼠模型的嗅觉系统功能障碍 小鼠FMRP基因Fmr1的表达令人惊讶的是，尽管嗅觉具有压倒性的重要性 对于啮齿动物来说，在Fmr1 KO小鼠身上进行这种感觉通道的研究很少。我们的目标，分为三个部分 目标将是： 目的1：验证Fmr1调控球内抑制性突触连接的假说。 目的2：验证Fmr1通过控制抑制作用调节球部局部网络活动的假说 突触连接。 目的3.验证Fmr1调节清醒行为中嗅觉行为和球振荡的假说 通过控制抑制性突触连接。 我们的研究将利用多种方法，包括脑片上的膜片钳记录， 超微结构分析、行为实验和活体电生理记录。小鼠模型 将包括全动物Fmr1 KO小鼠，这是FXS最广泛使用的小鼠模型，以及 有条件的KO和恢复小鼠，在其中Fmr1的表达被选择性和诱导地操纵在 表达GAD65的GABA能中间神经元。这种多学科的方法将使我们能够确定 由Fmr1表达改变引起的嗅觉功能障碍，水平从单一突触到 整个动物的行为，也将在不同水平观察到的变化联系起来。