Is learning blocked by saturation of synaptic weights in the hippocampus?

Long-term potentiation (LTP) has become a leading candidate mechanism for memory formation. The proposed link between LTP and memory rests primarily on a single type of behavioural evidence: disruption of learning by interventions that block critical steps in the induction of LTP. As such blockade may disrupt non-mnemonic functions also, the LTP-learning question should be approached with multiple strategies. One alternative approach is to determine whether hippocampus-dependent learning is blocked by saturation of hippocampal LTP before training. Early investigations found that spatial learning was impaired after cumulative LTP in dentate perforant-path synapses. Several groups failed to replicate these findings, but it is now clear that hippocampus-dependent spatial learning is disrupted only if LTP is saturated throughout the terminal field of the tetanized pathway. Moreover, to prevent compensatory modifications in the hippocampal network, a massed tetanization and training protocol may be required. The blockade of learning by repetition of the very same stimulus that induces LTP suggests that LTP-like modifications are necessary for memory encoding in the hippocampus.