Mechanisms of olfactory signal processing

嗅觉信号处理机制

• 批准号: 10209692
• 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/10209692
• 关键词: Animal Behavior; Animals; 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; GAD65 enzyme; Gene Expression; 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; base; behavioral impairment; cell type; classical conditioning; cognitive ability; experimental study; fly; granule cell; in vivo; interdisciplinary approach; male; mitral cell; mouse model; olfactory bulb; patch clamp; relating to nervous system; 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.

项目总结/摘要 （自闭症） 一个 个人 通信， 可以 谱系障碍 由于脆性X智力低下蛋白（FMRP）表达缺失而导致， 在X染色体上编码的mRNA结合蛋白，参与抑制蛋白质翻译。 患有FXS的患者在认知能力、社会交往和 和感官处理感觉处理的缺陷，通常被观察为超敏反应， 导致与FXS相关的其他缺陷（例如，社会互动）。的 脆性X综合征（FXS）是孤独症最常见的单基因原因 在人类身上。FXS 这一广泛目标 建议是检查嗅觉系统功能障碍的小鼠模型脆性X与减少 表达小鼠FMRP基因，Fmr1。令人惊讶的是，尽管嗅觉的重要性压倒一切， 对于啮齿类动物，在Fmr1基因敲除小鼠中进行的这种感觉方式的研究很少。我们的目标，分为三个 目标是： 目的1：验证Fmr1调节球内抑制性突触连接的假说。 目的2：验证Fmr1通过控制抑制性转录因子来调节鳞茎中的局部网络活动的假设。 突触连接 目标3.为了验证Fmr1调节嗅觉行为和清醒行为中延髓振荡的假设， 小鼠通过控制抑制性突触连接。 我们的研究将利用多种方法，包括在脑切片中进行膜片钳记录， 超微结构分析、行为实验和体内电生理记录。小鼠模型 将包括全动物Fmr 1 KO小鼠，这是最广泛使用的FXS小鼠模型，沿着 条件性KO和恢复小鼠，其中选择性地和诱导性地操纵Fmr1表达， 表达GAD 65的GABA能中间神经元。这种多学科的方法将使我们能够确定 嗅觉功能障碍是由Fmr1表达水平的改变引起的，从单个突触到 整个动物的行为，并联系在不同层次上观察到的变化。