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

一组特定的即刻早期基因(IEGs)由突触活动调节，在大脑发育过程中发挥重要作用，产生稳定和功能正常的皮质回路。IEG arg3.1已被证明与长期变化有关，并直接调节记忆下的突触过程和与新奇事件相关的编码。新的刺激涉及其中将呈现的刺激与先前编码的刺激进行比较以使其被认为是新的或熟悉的记忆组件。第一项研究将检测突触Arg 3.1的脑表达，与神经元c-fos相比，活动调节的IEG无论是对正常(C57BL/6)和自然失明(ZRDCT/AN)小鼠的新听觉刺激，还是对新的视觉刺激(C57BL/6)。这些IEG也将在反复暴露于相同刺激(熟悉)后以及在丰富或标准环境中饲养的动物中进行研究。先天失明的ZRDCT/AN小鼠是跨模式可塑性的极佳模型，因为听觉刺激已被证明产生正常视觉皮质的神经元激活，这种效应因环境的丰富而增强(Pichéet al.2004年)。这项工作的第二部分将检测暴露在新的视觉刺激下的鸽子大脑中的arg3.1和c-fos基因的表达，或者是在使用触摸屏呈现的刺激的更复杂的视觉强度辨别任务的初始学习或记忆阶段。这项工作将使我们能够阐明参与不同水平的感觉处理(感知、新刺激的编码、辨别学习和记忆)的基本大脑机制。这些研究还将使我们能够更好地理解在盲人或聋人身上观察到的一些跨模式感觉现象，并对感觉刺激对跨模式代偿的影响具有临床或治疗意义。

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.