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（由申请人提供）：经验塑造了大脑的功能能力，以适应个人的独特需求和环境。这种适应性变化的发生方式引起了极大的兴趣，因为它限制了个人的长期行为和能力。尽管这一点很重要，但基本的分子机制在很大程度上尚不清楚。该提案的目的是确定自适应可塑性期间神经基因表达的全球模式如何变化。研究的神经回路是谷仓猫头鹰声音定位途径。在这一途径中，对空间的听觉和视觉图被对齐并集成，以产生动物周围的统一表示。这些地图的共同注册可以通过将猫头鹰与水平移动的棱镜眼镜（棱镜）拟合来操纵。经过数周的棱镜经验，听觉空间映射了下丘（ICX）（ICX）和视觉底膜（OT）（OT）的外部核的图形，可自适应调整，恢复适当的比对和行为性能。这种自适应可塑性涉及地形适当的轴突发芽和突触发生。结构重塑的范围和持久性强烈表明，神经基因表达的变化是适应性调整的基础。为了鉴定关键的可塑性分子，我们将使用基因表达（SAGE）的序列分析在ICX中分析全基因组的表达。第一组实验的重点是少年猫头鹰的棱镜适应。自适应可塑性的功能阶段将通过听觉映射实验来定义。 SAGE分析将对从同一个人提取的听觉图的适应性和非适应部分进行。直接比较将揭示已知和新颖的神经基因，这些神经基因受棱镜经验差异调节。第二组实验将确定基因表达的变化，与棱镜适应的成年猫头鹰所显示的可塑性的增强相关。第三组实验涉及绘制差异调节转录物表达的时空模式，使用原位杂交对不同的神经元细胞类型进行绘制。我们希望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级哺乳动物。我们的长期目标是确定在正常学习过程中起着至关重要的作用的新型基因，并通过扩展，其故障可能有助于学习障碍和神经系统疾病，涉及神经可塑性失败。