The synaptic basis of learning in the auditory system

听觉系统学习的突触基础

• 批准号: 8463413
• 负责人: Wiliam McIntyre DeBello
• 金额: $ 29.33万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8463413
• 关键词: Address; Adolescent; Adult; Appearance; Attention; Auditory; Auditory system; Barn Owls; Behavioral; Biological; Brain; Cell Nucleus; Computer Simulation; Databases; Dendrites; Detection; Development; Exhibits; Foundations; Goals; Grant; Image; Individual; Inferior Colliculus; Knowledge; Learning; Learning Disorders; Length; Life; Location; Maps; Methods; Modeling; Movement; Mus; Neurons; Neurosciences; Optics; Pathway interactions; Pattern; Positioning Attribute; Relative (related person); Research Proposals; Resolution; Sensory; Series; Sound Localization; Stream; Strigiformes; Synapses; System; Testing; Tissues; Training; Transmission Electron Microscopy; Validation; base; design; experience; fascinate; neural circuit; novel; postsynaptic; presynaptic; prismatic spectacles; public health relevance; reconstruction; relating to nervous system; remediation; research study; skills; theories; therapy development; visual learning

DESCRIPTION (provided by applicant): The synaptic mechanisms that underlie the brain's remarkable capacity for learning remain unclear. One new model predicts that the acquisition and storage of learned skills involves the experience-driven clustering of co-active synapses onto short lengths of dendrite. Direct evidence for this synaptic clustering hypothesis is scant. This research proposal describes the first comprehensive tests of the model, to be provided by quantitative analysis of microanatomical changes in the barn owl auditory localization pathway. We recently showed that auditory-visual learning in juvenile owls involves selective adjustments in synaptic clustering on the dendrites of space-specific neurons, located within the inferior colliculus. In the first two sets of experiments we will determine whether similar changes occur in adults. Using multiple paradigms we will examine changes related both to the re-expression of normal circuitry and the acquisition of novel circuitry. The results will reveal the extent to which normal, enhanced and incremental training paradigms engage the synaptic clustering mechanism. In the third set of experiments we will examine a separate prediction of the model, whether non co-active synapses segregate on dendrites. The final set of experiments is designed to provide validation of these results at 'anatomical ground truth.' Specifically, we will use a newly developed high throughput method for serial section transmission electron microscopy to reconstruct the complete wiring diagram of the normal and learned circuits. These novel connectomes will be useful both for addressing the hypothesis-driven aims of this grant and for discovery-based approaches. Collectively, our experiments promise to reveal basic principles of synaptic reorganization that underlie the normal development and plasticity of sensory circuits, in both juvenile and adult brains. Such knowledge should prove invaluable for the long-term development of therapies aimed at the remediation of learning disorders.

描述（由申请人提供）：大脑出色学习能力的基础的突触机制尚不清楚。一种新模型预测，学习和存储学习技能涉及与经验驱动的共同激活突触的聚类到短长度的树突上。该突触聚类假设的直接证据很少。该研究建议描述了该模型的第一个综合测试，可以通过对谷仓猫头鹰听觉定位途径的微观变化进行定量分析提供。我们最近表明，少年猫头鹰中的听觉研究涉及在下丘脑内的空间特异性神经元的树突上进行突触聚类的选择性调整。在前两组实验中，我们将确定成人是否发生了类似的变化。使用多个范式，我们将检查与正常电路的重新表达和采集新电路有关的变化。结果将揭示正常，增强和增量训练范式在多大程度上涉及突触聚类机制。在第三组实验中，我们将检查模型的单独预测，无论非共同的突触是否在树突上分离。最后一组实验旨在在“解剖基础真理”中对这些结果进行验证。具体而言，我们将使用新开发的高通量方法来串行部分传输电子显微镜来重建正常电路和学习电路的完整接线图。这些新颖的连接组对于解决该赠款的假设驱动目的以及基于发现的方法将很有用。总的来说，我们的实验有望揭示突触重组的基本原理，这些原理是少年和成人大脑的正常发展和可塑性的基础。这种知识对于旨在补救学习障碍的疗法的长期发展应该证明是无价的。