Role of the immediate-early genes arg3.1 and c-fos in activity-dependent development of sensory systems and information processing in normal or congenitally blind animal models

立即早期基因 arg3.1 和 c-fos 在正常或先天性失明动物模型中感觉系统活动依赖性发育和信息处理中的作用

• 批准号: 53-2006
• 负责人: Miceli, Dom
• 金额: $ 2.26万
• 依托单位: Université du Québec à Trois-Rivières
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=361169
• 关键词: Role; immediate; early; genes; arg3.1

A specific set of immediate-early genes (IEGs) are regulated by synaptic activity and play an important role in brain development giving rise to stable and functioning cortical circuits. The IEG arg3.1 has been shown to be involved in long-term changes and to directly modulate synaptic processes underlying memory and the encoding of novelty-related events. Novel stimuli involve a memory component in which the presented stimulus is compared to previously encoded stimuli for it to be considered novel or familiar. The first study will examine the brain expression of synaptic arg 3.1, compared to neuronal c-fos, activity-regulated IEGs either to novel auditory stimulation of normal (C57BL/6) and naturally blind (ZRDCT/An) mice or to novel visual stimulation (C57BL/6). These IEGs will also be investigated after repeated exposure to the same stimuli (familiarisation) as well as in animals raised in either enriched or standard environments. The congenitally blind ZRDCT/An mouse serves as an excellent model for cross-modal plasticity as auditory stimulation has been shown to produce neuronal activation of what is normally visual cortex, an effect that is enhanced by environmental enrichment (Piché et al. 2004). The second part of the work will examine arg3.1 and c-fos gene expression in the pigeon brain following exposure to novel visual stimuli or during either initial learning or recall phases of more complex visual-intensity discrimination tasks using touchscreen presented stimuli. The work will allow us to elucidate basic brain mechanisms involved in different levels of sensory processing (perceptual, encoding of novel stimuli, discrimination learning and memory). The studies will also allow us to better understand some cross-modal sensory phenomena observed in blind or deaf humans and have clinical or therapeutic implications with regard to the effect of sensory stimulation on cross-modal compensation.

一组特定的即早基因（即早基因）受突触活动的调控，在大脑发育中发挥重要作用，产生稳定和功能的皮层回路。研究表明，IEG arg3.1参与了长期变化，并直接调节了记忆和新颖性相关事件编码的突触过程。新奇刺激包括一个记忆成分，在这个记忆成分中，呈现的刺激与先前编码的刺激相比较，从而被认为是新奇的或熟悉的。第一项研究将检查突触arg 3.1的大脑表达，与神经元c-fos相比，活动调节的eeg在正常小鼠（C57BL/6）和自然盲小鼠（ZRDCT/An）的新型听觉刺激或新型视觉刺激（C57BL/6）下的表达。这些脑电图也将在反复暴露于相同刺激（熟悉）以及在丰富或标准环境中饲养的动物中进行调查。先天失明的ZRDCT/An小鼠是一个很好的跨模态可塑性模型，因为听觉刺激已被证明会产生通常是视觉皮层的神经元激活，这种效果会因环境丰富而增强（pich<s:1>等人，2004）。研究的第二部分将研究arg3.1和c-fos基因在暴露于新的视觉刺激或在使用触摸屏呈现的刺激进行更复杂的视觉强度识别任务的初始学习或回忆阶段时在鸽子大脑中的表达。这项工作将使我们能够阐明涉及不同层次感觉处理（知觉、新刺激编码、辨别、学习和记忆）的基本大脑机制。这些研究还将使我们更好地理解在盲人或聋人身上观察到的一些跨模态感觉现象，并对感觉刺激对跨模态补偿的影响具有临床或治疗意义。