Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mζ (PKMζ)
Metaplasticity governs compartmentalization of synaptic tagging and capture through brain-derived neurotrophic factor (BDNF) and protein kinase Mζ (PKMζ)
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DOI：
10.1073/pnas.1016849108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Korte, Martin
中科院分区：
文献类型：
--
作者：
Sajikumar, Sreedharan;Korte, Martin
活动依赖性突触可塑性被广泛认为是学习和记忆的细胞相关。据信，不同突触输入之间的关联性可以将短暂形式的突触可塑性（< 3小时）转变为持久形式的突触可塑性。突触标记和捕获（STC）可能能够解释这种异突触支持，因为它区分了突触标记的局部机制和负责可塑性相关蛋白（PRP）合成的细胞范围内的机制。STC启动存储过程中，只有当突触标签的强度和必要的蛋白质的局部浓度高于一定的可塑性阈值。我们提出的证据表明，通过激活代谢型谷氨酸受体的启动刺激，通过产生蛋白激酶M ζ（PKM ζ）作为PRP通过局部蛋白质合成，大大增加了功能可塑性的“阈值范围”。此外，我们的研究结果暗示BDNF作为PRP，这是强制性的建立突触加强和减弱之间的交叉捕获，而新产生的PKM。专门建立长时程增强的突触标记。最有趣的是，我们在这里表明，STC仅限于特定的树突状车厢，这些车厢包含“突触簇”具有不同的可塑性阈值。我们的研究结果表明，在一个树突隔室本身的稳态过程存在调整可塑性阈值。这些簇的作用范围可以通过亚塑性过程来改变，亚塑性过程将独立于同一枝晶上的其他簇而作用于簇。然后，这些簇将准备突触网络以形成长期记忆。
Activity-dependent synaptic plasticity is widely accepted to be the cellular correlate of learning and memory. It is believed that associativity between different synaptic inputs can transform short-lasting forms of synaptic plasticity (< 3 h) to long-lasting ones. Synaptic tagging and capture (STC) might be able to explain this heterosynaptic support, because it distinguishes between local mechanisms of synaptic tags and cell-wide mechanisms responsible for the synthesis of plasticity-related proteins (PRPs). STC initiate storage processes only when the strength of the synaptic tag and the local concentration of essential proteins are above a certain plasticity threshold. We present evidence that priming stimulation through the activation of metabotropic glutamate receptors substantially increases the "range of threshold" for functional plasticity by producing protein kinase M zeta (PKM zeta) as a PRP through local protein synthesis. In addition, our results implicate BDNF as a PRP which is mandatory for establishing cross-capture between synaptic strengthening and weakening, whereas the newly generated PKM. specifically establishes synaptic tagging of long-term potentiation. Most intriguingly, we show here that STC are confined to specific dendritic compartments and that these compartments contain "synaptic clusters" with different plasticity thresholds. Our results suggest that within a dendritic compartment itself a homeostatic process exists to adjust plasticity thresholds. The range in which these clusters operate can be altered by processes of metaplasticity, which will operate on the cluster independently of other clusters at the same dendrite. These clusters will then prepare the synaptic network to form long-term memories.