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

Abstract

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.

Bidirectional Modulation of Hippocampal Long-Term Potentiation under Stress and No-Stress Conditions in Basolateral Amygdala-Lesioned and Intact Rats

“…A single exposure to an aversive stimulation can be sufficient for corticosterone-mediated memory consolidation (Cordero et al, 2003), which is long lasting (Diamond et al, 2004;Gale et al, 2004;Izquierdo and Cammarota, 2004;Müller Igaz et al, 2004). This is in accordance with our result that briefly pretrained animals show no LTP reinforcement, although the corticosterone response to the test situation is similar compared with naive animals.…”

Neuroprotection and Enhancement of Learning and Memory by BF-7

“…12,33) Beyond transient functional declines, severe physiologic, chemical, and environmental stress gives rise to anatomic and physiologic brain damage. 34,35) The discovery of methods to protect the brain would thus be meaningful.…”

Chronic enhancement of CREB activity in the hippocampus interferes with the retrieval of spatial information

“…In a subset of the animals (19 VP16-CREB high and 19 control littermates), the housing conditions were switched after P2 (VP16-CREB high SC!EE = 10, VP16-CREB high EE!SC = 9, control SC!EE = 9, and control EE!SC = 10). A third probe trial ( (Martin and Morris 2002;Diamond et al 2004). Interestingly, we have also observed that the expression of VP16-CREB bypassed the requirement for de novo gene expression associated with longterm memory formation in contextual and cued fear conditioning tasks, suggesting that CREB-dependent gene expression can be sufficient for fear memory consolidation (Viosca et al 2009).…”

“…The effects in fear memory consolidation and spatial memory retrieval observed in mice with enhanced CREB activity might have a physiological correlate in normal behaving animals. Memory reinforcement and retroactive amnesia are two features associated with the formation of flashbulb memory during highly stressful experiences (Diamond et al 2004(Diamond et al , 2006. During such events a number of neuromodulator molecules are widespread released within several forebrain areas.…”