Redondo, Roger L., Okuno, Hiroyukki, Dr., Spooner, Patrick A., Frenguelli, Bruno G., Bito, Haruhiko and Morris, R. G. M. (Richard G. M.) (2010) Synaptic tagging and capture : differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation. Journal of Neuroscience, Vol.30 (No.14). pp. 4981-4989. doi:10.1523/JNEUROSCI.3140-09.2010

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Abstract

Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting ~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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Synapses -- Research, Hippocampus (Brain), Neuroplasticity -- Research, Adaptation (Physiology)
Journal or Publication Title:	Journal of Neuroscience
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Official Date:	7 April 2010
Dates:	Date Event 7 April 2010 Published
Volume:	Vol.30
Number:	No.14
Number of Pages:	9
Page Range:	pp. 4981-4989
DOI:	10.1523/JNEUROSCI.3140-09.2010
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Human Frontiers Science Program (HFSP), Volkswagenstiftung (VWS), Medical Research Council (Great Britain) (MRC), Japan. Monbu Kagakushō [Japan. Ministry of Education, Culture, Sports, Science and Technology] (MK), Japan. Kōsei Rōdōshō (KR), Takeda Kagaku Shinkō Zaidan [Science Foundation], Yamada Kagaku Shinkō Zaidan (YKSZ)

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