Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 19, Pages 5190-5199Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5049-06.2007
Keywords
CaMKII; depotentiation; hippocampus; LTP; maintenance; memory
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Funding
- NINDS NIH HHS [R01 NS050944, R01 NS027337] Funding Source: Medline
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Long-term potentiation (LTP) is an activity-dependent strengthening of synapses that is thought to underlie memory storage. Ca2+/ calmodulin-dependent protein kinase II (CaMKII) has been a leading candidate as a memory molecule because it is persistently activated after LTP induction and can enhance transmission. Furthermore, a mutation that blocks persistent activation blocks LTP and forms of learning. However, direct evidence for a role of the kinase in maintaining synaptic strength has been lacking. Here, we show that a newly developed noncompetitive inhibitor of CaMKII strongly reduces synaptic transmission in the CA1 region of the hippocampal slice. This occurs through both presynaptic and postsynaptic action. To study the role of CaMKII in the maintenance of LTP, inhibitor was applied after LTP induction and then removed. Inhibition occurred in both LTP and control pathways but only partially recovered. The nonrecovering component was attributable primarily to a postsynaptic change. To test whether nonrecovery was attributable to a persistent reversal of LTP, we first saturated LTP and then transiently applied inhibitor. This procedure allowed additional LTP to be induced, indicating a reversal of an LTP maintenance mechanism. This is the first procedure that can reverse LTP by chemical means and suggests that a component of synaptic memory is attributable to CaMKII. The procedure also enhanced the LTP that could be induced in the control pathway, consistent with the idea that CaMKII is involved in controlling basal synaptic strength, perhaps as a result of LTP that occurred in vivo.
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