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Metaplasticity of synaptic tagging and capture and its implications for maintaining long-term memory in normal and diseased neural networks

突触标记和捕获的可塑性及其对维持正常和患病神经网络长期记忆的影响

基本信息

批准号：
112578143
负责人：
Professor Dr. Martin Korte
金额：
--
依托单位：
Department of Physiology
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2008
资助国家：
德国
起止时间：
2007-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/112578143?language=en
关键词：
Metaplasticity synaptic tagging capture its

项目摘要

Synaptic tagging and capture (STC) is one of the prominent models of associative memory formation at the cellular level. In line with this STC hypothesis, weak memory formation creates time-dependent synaptic tags/marks that might capture memory related proteins available due to a parallel strong memory input in a nearby synaptic network. This process results in the consolidation of the respective weak memory. One of us was involved in the identification of some of the key mechanisms and molecules in STC (Sajikumar et al., 2005b; Sajikumar et al., 2007). However, it is still unclear how memory consolidated through STC erases with time. We propose a new mechanism for the erasure of memory in neural networks: synaptic competition / distribution phase of memory. According to our hypothesis, a neuronal population will compete for memory proteins if the availability of these proteins is scarce, and the competing partners exhibit nearly similar plasticity thresholds. In consequence, consolidated memories are erased over the time. On the other hand, our model predicts that a synaptic population, which is able to survive synaptic competition, will have a better chance to code long-term memory without disruption. Understanding the cellular mechanisms of synaptic competition is important for finding appropriate therapeutic agents for preventing memory loss. In our studies, we will use ryanodine receptor (RYR) or metabotropic receptor mediated metaplasticity and analyze the role of metaplasticity induced protein PKMzeta for preventing synaptic competition. Understanding the phase and properties of competition of memory will provide new insight into the onset of age related dementia and the puzzling question of why some people have sharp memory irrespective of age and why others have not leading to Alzheimers disease (AD). In addition, we will explore the possibility of using metaplasticity as a therapeutic strategy for improving memory by targeting the neural network level in Alzheimers disease.

突触标记和捕获（STC）是在细胞水平上形成联想记忆的重要模型之一。与STC假说一致，弱记忆形成产生时间依赖性突触标签/标记，其可能捕获由于附近突触网络中的并行强记忆输入而可用的记忆相关蛋白。这个过程导致各自弱记忆的巩固。我们中的一个参与了STC中一些关键机制和分子的鉴定（Sajikumar等人，2005 b; Sajikumar等人，2007年）。然而，目前还不清楚如何巩固通过STC的内存擦除随着时间的推移。我们提出了一种新的机制擦除记忆的神经网络：突触竞争/分配阶段的记忆。根据我们的假设，如果记忆蛋白质的可用性是稀缺的，并且竞争伙伴表现出几乎相似的可塑性阈值，神经元群体将竞争这些蛋白质。因此，巩固的记忆随着时间的推移而被擦除。另一方面，我们的模型预测，能够在突触竞争中生存下来的突触群体将有更好的机会在不中断的情况下编码长期记忆。了解突触竞争的细胞机制对于寻找适当的治疗药物来预防记忆丧失非常重要。本研究将利用Ryanodine受体（Ryanodine receptor，RYR）或代谢型受体介导的后可塑性，分析后可塑性诱导蛋白PKMzeta在阻止突触竞争中的作用。了解记忆竞争的阶段和性质将为老年性痴呆的发病提供新的见解，以及为什么有些人无论年龄大小都有敏锐的记忆力，而另一些人却没有导致阿尔茨海默病（AD）的令人困惑的问题。此外，我们将探索使用metaplasticity作为一种治疗策略，通过针对阿尔茨海默病的神经网络水平改善记忆的可能性。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Different compartments of apical CA1 dendrites have different plasticity thresholds for expressing synaptic tagging and capture.

顶端 CA1 树突的不同区室具有不同的表达突触标记和捕获的可塑性阈值

DOI：
10.1101/lm.2095811
发表时间：
2011
期刊：
Learning & memory
影响因子：
2
作者：
Sajikumar
通讯作者：
Sajikumar

Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mζ (PKMζ)

DOI：
10.1073/pnas.1016849108
发表时间：
2011-02-08
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Sajikumar, Sreedharan;Korte, Martin
通讯作者：
Korte, Martin

Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture.