STRUCTURAL AND FUNCTIONAL SYNAPTIC CHANGES IN LEARNING

学习中的结构和功能突触变化

• 批准号: 2379742
• 负责人: YURI GEINISMAN
• 金额: $ 17.36万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2379742
• 关键词: behavioral /social science research tag; conditioning; electrophysiology; hippocampus; histology; laboratory rabbit; learning; membrane potentials; molecular psychobiology; neural information processing; neural plasticity; neuroanatomy; nictitating membrane; synapses; tissue /cell culture

The problem of how information is stored in the brain is fundamental for neurobiology. The overall goal of our research is to elucidate whether the mechanism of learning and memory involves structural modifications of synaptic connections. Although historically it has been believed to be the case, there is no unequivocal experimental evidence to support such a notion. The results of previous electron microscopic studies of learning-induced synaptic restructuring in the vertebrate brain need to be reevaluated since they were obtained using biased technical approaches. We now propose to reexamine the issue with the aid of modern unbiased techniques for synapse quantitation. Recently, we identified a novel morphological subtype of synapses characterized by multiple, completely partitioned transmission zones. The efficacy of impulse transmission is expected to be unusually high in a synapse having several transmission zones, rather than only one, as is usual. Since an augmented synaptic efficacy is widely regarded as a basic mechanism of learning and memory, we developed a model of learning-induced structural synaptic plasticity, the pivotal element of which is the formation of additional synapses with multiple transmission zones from other preexisting synaptic junctions. The proposed experiments are designed to test the predictions of this model by examining alterations in synaptic efficacy and ultrastructure associated with classical conditioning. We will utilize the paradigm of trace conditioning of the rabbit nictitating membrane response which is crucially dependent on the integrity of the hippocampal formation. Eyeblink conditioning results in an augmented synaptic responsiveness of the majority of hippocampal neurons, and this behavioral paradigm offers the important opportunity to differentiate learning-specific from activity-related changes by comparing conditioned, pseudoconditioned and naive animals. Hippocampal slices maintained in vitro will be used to detect conditioning-specific alterations in synaptic potentials with extracellular recordings and in the number of synaptic contacts with the unbiased stereological disector technique. The results to be obtained will unequivocally show if classical conditioning is accompanied by changes in the number of any morphological subtype of synapses and if these changes correlate with conditioning-specific alterations in synaptic efficacy. Such data are essential for a better understanding of mechanisms of learning and memory, as well as of the pathogenesis of memory disorders such as Alzheimer's disease.

信息如何在大脑中存储的问题对于人类来说至关重要。 神经生物学。 我们研究的总体目标是阐明是否 学习和记忆的机制涉及结构修饰 突触连接。 尽管历史上人们一直认为 事实如此，没有明确的实验证据支持 这样的观念。 之前的电子显微镜研究结果 脊椎动物大脑中学习引起的突触重组需要 由于它们是使用有偏见的技术获得的，因此需要重新评估 接近。 我们现在建议借助现代技术重新审视这个问题 突触定量的无偏技术。 最近，我们确定 一种新的突触形态亚型，其特征是多个， 完全划分的传输区域。 冲动的功效 在具有多个突触的突触中，传输预计会异常高 传输区域，而不是像往常那样只有一个传输区域。 自从 增强突触功效被广泛认为是一种基本机制 学习和记忆，我们开发了一个学习诱发的结构模型 突触可塑性，其关键要素是形成 具有来自其他区域的多个传输区域的附加突触 预先存在的突触连接。 所提出的实验设计 通过检查变化来测试该模型的预测 与经典相关的突触功效和超微结构 调理。 我们将利用微量调节的范式 兔子瞬膜反应主要取决于 海马结构的完整性。 眨眼调理结果 大部分海马的突触反应性增强 神经元，这种行为范式提供了重要的机会 通过以下方式区分特定于学习的变化和与活动相关的变化 比较条件动物、假条件动物和幼稚动物。 海马 体外保存的切片将用于检测条件特异性 细胞外记录和突触电位的改变 与无偏立体解剖学的突触接触数量 技术。 获得的结果将明确表明： 经典条件反射伴随着任何数量的变化 突触的形态亚型以及这些变化是否与 突触功效的条件特异性改变。 此类数据是 对于更好地理解学习机制和 记忆以及记忆障碍的发病机制，例如 阿尔茨海默病。