Competitive Interactions Between Endogenous LTD and LTP in the Hippocampus Underlie the Storage of Emotional Memories and Stress-induced Amnesia

This speculative review serves two purposes. First, it as an extension of the ideas we developed in a previous review (Diamond et al., Hippocampus, 2004;14:281-291), and second, it is a rebuttal to Abraham's (Hippocampus, 2004;14:675-676) critique of that review. We had speculated on the functional significance of the finding that post-training LTP induction produces retrograde amnesia. We noted the similarities between the findings that strong tetanizing stimulation can produce LTP and retrograde amnesia, and that a strong emotional experience can produce a long-lasting memory and retrograde amnesia, as well. The commonalities between LTP induction and emotional learning provided the basis of our hypothesis that an emotional experience generates endogenous LTD/depotentiation, which reverses synaptic plasticity formed during previous learning experiences, and endogenous LTP, which underlies the storage of new information. Abraham raised several concerns with our review, including the criticism that our speculation "falters because there is no evidence that stress causes LTD or depotentiation," and that research on stress and hippocampus has "failed to report any LTP-like changes." Abraham's points are well-taken because stress, in isolation, does not appear to generate long-lasting changes in baseline measures of hippocampal excitability. Here, within the context of a reply to Abraham's critique, we have provided a review of the literature on the influence of stress, novelty, fear conditioning, and the retrieval of emotional memories on cognitive and physiological measures of hippocampal functioning. An emphasis of this review is our hypothesis that endogenous forms of depotentiation, LTD and LTP are generated only when arousing experiences occur in conjunction with memory-related activation of the hippocampus and amygdala. We conclude with speculation that interactions among the different forms of endogenous plasticity underlie a form of competition by synapses and memories for access to retrieval resources.