Weak before strong: dissociating synaptic tagging and plasticity-factor accounts of late-LTP.

Experiments were conducted using hippocampal slices in vitro to compare two accounts of the mechanisms by which input-specific protein synthesis-dependent long-term potentiation (late-LTP) may be realised. The synaptic tag hypothesis (Frey and Morris, 1997) predicts that the expression of early-LTP following a weak tetanus can be stabilised into late-LTP by subsequent strong tetanisation of a separate pathway, provided the interval between the two tetanisation episodes is within the decay time-course of a putative synaptic tag. An alternative plasticity-factors hypothesis requires that strong tetanisation should always precede weak tetanisation for stabilisation of early-LTP to occur. Our results indicate that weak tetanisation of pathway S2 at intervals of 5 min or 1 h prior to strong tetanisation on pathway S1 does result in late-LTP on pathway S2. Stabilisation was weaker or did not occur at intervals of 2 and 4 h. This stabilisation effect was shown to depend on protein synthesis during the strong tetanisation of S1. These findings uphold a key prediction of the synaptic tag hypothesis and have implications for the functional role of synaptic tagging for cortical plasticity.