Stress generates emotional memories and retrograde amnesia by inducing an endogenous form of hippocampal LTP

Models of the neurobiology of memory have been based on the idea that information is stored as distributed patterns of altered synaptic weights in neuronal networks. Accordingly, studies have shown that post‐training treatments that alter synaptic weights, such as the induction of long‐term potentiation (LTP), can interfere with retrieval. In these studies, LTP induction has been relegated to the status of a methodological procedure that serves the sole purpose of disturbing synaptic activity in order to impair memory. This perspective has been expressed, for example, by Martin and Morris (2002: Hippocampus 12:609–636), who noted that post‐training LTP impairs memory by adding “behaviorally meaningless” noise to hippocampal neural networks. However, if LTP truly is a memory storage mechanism, its induction should represent more than just a means with which to disrupt memory. Since LTP induction produces retrograde amnesia, the formation of a new memory should also produce retrograde amnesia. In the present report, we suggest that one type of learning experience, the storage of fear‐related (i.e., stressful) memories, is consistent with this prediction. Studies have shown that stress produces potent effects on hippocampal physiology, generates long‐lasting memories, and induces retrograde amnesia, all through mechanisms in common with LTP. Based on these findings, we have developed the hypothesis that a stressful experience generates an endogenous form of hippocampal LTP that substitutes a new memory representation for preexisting representations. In summary, our hypothesis implicates the induction of endogenous synaptic plasticity by stress in the formation of emotional memories and in retrograde amnesia. © 2004 Wiley‐Liss, Inc.