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.

信息是如何储存在大脑中的问题， 神经生物学 我们研究的总体目标是阐明 学习和记忆的机制包括结构的改变 突触连接的方式。 尽管历史上人们认为 事实上，没有明确的实验证据支持 这样一个概念。 以前的电子显微镜研究结果表明， 脊椎动物大脑中学习诱导的突触重组需要 因为它们是使用有偏见的技术 接近。 我们现在建议借助现代科学重新审视这一问题。 突触定量的无偏技术。 最近，我们发现 一种新的突触形态亚型， 完全隔离的传输区域。 冲动的功效 预期在具有多个突触的突触中， 传输区，而不是像往常一样只有一个。 因为一个 增强的突触功效被广泛认为是 学习和记忆，我们开发了一个学习诱导的结构模型， 突触可塑性，其中的关键因素是形成 具有多个传输区的额外突触 预先存在的突触连接 所提出的实验设计 为了检验这个模型的预测， 突触效能和超微结构与经典 条件反射 我们将利用的范式跟踪条件反射的 兔瞬膜反应，这是至关重要的依赖于 海马结构的完整性 眨眼条件反射结果 大部分海马神经元的突触反应增强， 神经元，这种行为模式提供了重要的机会， 通过以下方式区分学习特定的变化和活动相关的变化： 比较条件化、假条件化和幼稚动物。 海马 体外保存的切片将用于检测条件特异性 细胞外记录的突触电位的改变， 无偏体视学分割器的突触接触数 法 获得的结果将明确表明，如果 经典条件作用伴随着任何 突触的形态亚型，如果这些变化与 突触效能的条件特异性改变。 这些数据 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， 老年痴呆症