Neural Gene Expression During Adaptive Plasticity

适应性可塑性期间的神经基因表达

• 批准号: 6534625
• 负责人: Wiliam McIntyre DeBello
• 金额: $ 29.7万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-16 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534625
• 关键词: auditory stimulus; behavioral /social science research tag; biological signal transduction; brain mapping; environmental adaptation; ethology; gene environment interaction; gene expression; genetic library; genetic mapping; genetic transcription; in situ hybridization; inferior colliculus; membrane potentials; neural plasticity; owls; polymerase chain reaction; protein localization; protein structure function; serial analysis of gene expression; sound perception; space perception; superior colliculus; vision aid; visual perception

DESCRIPTION (provided by applicant): Experience shapes the functional capacity of the brain to suit the unique needs and environment of the individual. How such adaptive change occurs is of great interest as it circumscribes the individual's long-term behavior and capabilities. Despite this importance, the underlying molecular mechanisms are largely unknown. The goal of this proposal is to identify how the global pattern of neural gene expression changes during adaptive plasticity. The neural circuit under study is the barn owl sound localization pathway. Within this pathway, auditory and visual maps of space are aligned and integrated to yield a unified representation of the animal's surround. The co-registration of these maps can be manipulated by fitting owls with horizontally displacing prismatic spectacles (prisms). After several weeks of prism experience, the auditory space maps in the external nucleus of the inferior colliculus (ICX) and optic tectum (OT) adaptively adjust, restoring proper alignment and behavioral performance. This adaptive plasticity involves topographically appropriate axonal sprouting and synaptogenesis. The scope and persistence of structural remodeling strongly suggest that changes in neural gene expression underlie adaptive adjustment. To identify the crucial plasticity molecules, we will analyze genome-wide expression in the ICX and OT using serial analysis of gene expression (SAGE). The first set of experiments focuses on prism adaptation in juvenile owls. Functional phases of adaptive plasticity will be defined by auditory mapping experiments. SAGE analysis will be performed on adapted and non-adapted parts of the auditory map extracted from the same individual. Direct comparison will reveal the known and novel neural genes that are differentially regulated by prism experience. The second set of experiments will identify changes in gene expression associated with the enhanced capacity for plasticity displayed by prism-adapted adult owls. The third set of experiments involves mapping the spatio.-temporal patterns of expression of differentially regulated transcripts to different neuronal cell types using in situ hybridization. We expect that the data obtained by this approach will be broadly applicable to higher mammals including humans. Our long-term objective is to identify novel genes that play crucial roles during normal learning processes, and by extension, whose malfunction may contribute to learning disabilities and neurological disorders that involve a failure in neuroplasticity.

描述(申请人提供)：经验塑造大脑的功能能力，以适应个人的独特需求和环境。这种适应性变化是如何发生的，人们对此非常感兴趣，因为它限制了个人的长期行为和能力。尽管这很重要，但其潜在的分子机制在很大程度上是未知的。这项建议的目标是确定在适应性可塑性过程中神经基因表达的全球模式是如何变化的。正在研究的神经回路是谷仓猫头鹰声音定位通路。在这条路径中，听觉和视觉空间地图被排列和整合，以产生动物周围环境的统一表示。这些地图的联合配准可以通过为猫头鹰配备水平移位的棱镜(棱镜)来操纵。经过几周的棱镜实验，下丘外核(ICx)和视顶盖(OT)的听觉空间图进行了适应性调整，恢复了正确的排列和行为表现。这种适应性可塑性包括适当的局部轴突萌发和突触发生。结构重塑的范围和持续性强烈表明，神经基因表达的变化是适应性调整的基础。为了确定关键的可塑性分子，我们将使用基因表达序列分析(SAGE)来分析ICx和OT中的全基因组表达。第一组实验的重点是幼年猫头鹰对棱镜的适应。适应性可塑性的功能阶段将通过听觉映射实验来确定。SAGE分析将对从同一个体提取的听觉映射的适应部分和非适应部分进行分析。直接比较将揭示已知和新的神经基因，这些基因受棱镜经验的差异调控。第二组实验将确定与棱镜适应成年猫头鹰表现出的增强可塑性相关的基因表达的变化。第三组实验涉及使用原位杂交将差异调控转录本的时空表达模式映射到不同类型的神经细胞。我们预计，通过这种方法获得的数据将广泛适用于包括人类在内的高等哺乳动物。我们的长期目标是确定在正常学习过程中发挥关键作用的新基因，进而，其功能障碍可能导致学习障碍和神经可塑性障碍。