2010年4月
Synaptic Tagging and Capture: Differential Role of Distinct Calcium/Calmodulin Kinases in Protein Synthesis-Dependent Long-Term Potentiation
JOURNAL OF NEUROSCIENCE
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- 巻
- 30
- 号
- 14
- 開始ページ
- 4981
- 終了ページ
- 4989
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1523/JNEUROSCI.3140-09.2010
- 出版者・発行元
- SOC NEUROSCIENCE
Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting similar to 3 h (called early-LTP) will maintain a longer-lasting change in efficacy (late-LTP) if the weak tetanization occurs shortly before or after strong tetanization of an independent, but convergent, set of synapses in CA1. The synaptic tagging and capture hypothesis explains this heterosynaptic influence on persistence in terms of a distinction between local mechanisms of synaptic tagging and cell-wide mechanisms responsible for the synthesis, distribution, and capture of plasticity-related proteins (PRPs). We now present evidence that distinct CaM kinase (CaMK) pathways serve a dissociable role in these mechanisms. Using a hippocampal brain-slice preparation that permits stable long-term recordings in vitro for >10 h and using hippocampal cultures to validate the differential drug effects on distinct CaMK pathways, we show that tag setting is blocked by the CaMK inhibitor KN-93 (2-[ N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl) amino-N-(4-chlorocinnamyl)-N- methylbenzylamine) that, at low concentration, is more selective for CaMKII. In contrast, the CaMK kinase inhibitor STO-609 [7H-benzimidazo(2,1-a)benz(de) isoquinoline-7-one-3-carboxylic acid] specifically limits the synthesis and/or availability of PRPs. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders and test stimulation over long periods of time after LTP induction enable a pharmacological dissociation of these distinct roles of the CaMK pathways in late-LTP and so provide a novel framework for the molecular mechanisms by which synaptic potentiation, and possibly memories, become stabilized.
- リンク情報
- ID情報
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- DOI : 10.1523/JNEUROSCI.3140-09.2010
- ISSN : 0270-6474
- PubMed ID : 20371818
- Web of Science ID : WOS:000276414800018