Is LTP in the hippocampus a useful model for learning-related alterations in gene expression?

It is well established that the formation of long-term memory requires de novo protein synthesis. Altered gene expression is therefore critical in the signal transduction cascade activated by the learning experience. Long-term potentiation (LTP) is a mnemonic model in which particular patterns of activation of incoming excitatory fibers (representing the learning experience) may induce long-lasting enhancement of the communication between the involved pre- and post-synapses (representing the memory). Therefore, cellular and molecular mechanisms of LTP have been extensively studied under the assumption that their understanding will contribute to our comprehension of the mechanisms underlying memory formation. In recent years, however, this analogy has been challenged by reports of inconsistency between LTP and memory. Here we assess LTP in the hippocampus as a model system to study spatial memory-related alterations in gene expression. We focus on three molecular families that are likely to play a role in synaptic plasticity: (1) synaptic communication related proteins; (2) signal transduction machinery; and (3) growth factors. Reviewing first the literature on LTP and then behavioral research we found both consistent and inconsistent findings regarding the LTP/memory linkage. The importance of restricting the discussion to both a learning phase and a brain (sub)structure, as well as of incorporating more physiological LTP stimulation protocols, is discussed. We conclude that while LTP is indeed limited as a model of memory, a careful use of it as a model system of synaptic plasticity is fruitful and productive in screening out candidate memory-related genes.