Plasticity in Unitary Synaptic Connections

单一突触连接的可塑性

• 批准号: 6460945
• 负责人: Vernon Daniel MADISON
• 金额: $ 32.12万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460945
• 关键词: NMDA receptors; binding proteins; depression; emotions; fear; hippocampus; laboratory rat; learning; long term potentiation; memory; neural plasticity; neurons; neurophysiology; phosphorylation; protein structure function; pyramidal cells; receptor expression; synapses; tissue /cell culture

DESCRIPTION (provided by applicant): Synaptic plastic processes such as long-term potentiation (LTP) and long-term depression (LTD) play a central role in virtually all models that seek to explain learning and memory at a cellular level. Beyond even that, LTP and LTD are found in many brain areas and have been proposed to play a role in a wide range of neural functions and disorders. Neural functions from fear and emotion, through memory to addiction have been proposed to have a basis in these plastic processes. Therefore, the understanding of the mechanisms that underlie this plasticity will provide wide-ranging benefits not only to understanding normal brain function, but also to many neurological disorders. The study of LTP and LTD have been plagued by conflicting theories and experimental results that has in many cases slowed progress in understanding the underlying mechanism of these neuronal properties. Much of this confusion, we believe, has arisen from technical limitations of experiments that have, by necessity, relied exclusively on measures of synaptic plasticity in large populations of synapses. Since synapses can be found in a variety of plastic states, e.g. naive, potentiated, depressed, and populations of synapses almost certainly contain all these states and more, experimental manipulations may provide confusing results. Much as patch clamp recording, where the activity of a small number of ion channels could be recorded in isolation, revolutionized the study of ion channel function. the field of synaptic plasticity could benefit from experiments where very small numbers of synapses could be selectively studied and manipulated. In this proposal, we employ a method where we can record the activity of small numbers of synapses (1-10) identify their plastic state, and experimentally manipulate that state. By doing so, we can study the transitions between different plastic states in cases where we know the history of the synapses under study. In our preliminary studies, we have already clarified several issues relating to the mechanisms of synaptic plasticity and expect that the experiments in this proposal will greatly expand our knowledge of these mechanisms.

描述（由申请人提供）：突触塑性过程，例如 长时程增强（LTP）和长时程抑制（LTD）发挥核心作用 几乎所有试图解释细胞学习和记忆的模型 等级。除此之外，LTP 和 LTD 存在于大脑的许多区域，并且 已被认为在广泛的神经功能和疾病中发挥作用。 从恐惧和情绪到记忆到成瘾的神经功能已被 建议在这些塑料工艺中有基础。因此， 了解这种可塑性背后的机制将提供 不仅对了解正常的大脑功能有广泛的好处，而且 导致许多神经系统疾病。 LTP和LTD的研究一直受到以下问题的困扰 相互矛盾的理论和实验结果在许多情况下减缓了 在理解这些神经元的潜在机制方面取得了进展 特性。我们认为，这种混乱很大程度上是由技术引起的 实验的局限性，必然完全依赖于 大量突触群体中突触可塑性的测量。自从 突触可以处于多种可塑状态，例如天真、坚强、 抑郁症，突触群体几乎肯定包含所有这些 状态等等，实验操作可能会提供令人困惑的结果。很多 作为膜片钳记录，其中少量离子通道的活动 可以单独记录，彻底改变了离子通道的研究 功能。突触可塑性领域可以从以下实验中受益 可以选择性地研究和操纵极少量的突触。在 在这个提案中，我们采用了一种可以记录小型活动的方法 突触数量 (1-10) 确定其可塑状态，并通过实验 操纵该状态。通过这样做，我们可以研究之间的转变 在我们知道突触历史的情况下不同的可塑状态 正在研究中。在我们的初步研究中，我们已经澄清了几个问题 与突触可塑性机制有关的问题，并期望 该提案中的实验将极大地扩展我们对这些的了解 机制。