Resetting of 'synaptic tags' is time- and activity-dependent in rat hippocampal CA1 in vitro.

We have recently proposed that the maintenance of hippocampal long-term potentiation (LTP) and depression depends on at least two required processes: induction of LTP must set (1) process-specific 'synaptic tags' which capture (2) process-unspecific plasticity-related proteins (PRPs), synthesized via a heterosynaptic interaction [Neurobiol Learn Mem 82 (2004) 12]. The 'tag' as well as the PRPs are characterized by a relatively short half-life of several minutes up to a few hours before they degrade most likely by processes such as dephosphorylation. The question now arose whether the 'tags' can also be reset in an activity-dependent manner, thus preventing the processing of PRPs with the result of transient short-lasting plasticity. Here we have investigated this topic during early-LTP and found that low-frequency stimulation shortly after early-LTP-induction (5 min) resets the 'tag' or the 'tag complex' of macromolecules preventing any lasting forms of LTP and thus, preventing the formation of a memory trace.