Updating of memories during memory consolidation

点击翻译按钮获取中文摘要

SummaryAnimals, including humans, learn by exploring the environment and assessing the predictive value of a particular experience by trial and error. This basic form of learning, called associative conditioning, enables animals to adaptively respond to sensory signals that are associated with reward or punishment. By learning such an association, an animal can more effectively locate and exploit food resources or avoid threats. Following the initial formation of an associative memory there is a period of consolidation, during which the memory becomes progressively more permanent. We showed that during consolidation there are brief periods of amnesia during which the progression to long-term memory storage can be blocked or altered by unanticipated changes in the sensory environment. Recently we provided further evidence for this flexibility of consolidation by showing that a more important or recent experience during these lapse periods can fundamentally change the fate of the original association. Indeed it can result in the replacement of the first association with a second one. Although lapses may look like non-adaptive deficits in memory storage, we claim that they are important in providing opportunities for alteration of the memory trace. The updating of the memory at lapse points has the advantage of preventing the costly process of consolidation of an obsolete memory while providing opportunity for new or more important experience to be incorporated into or even replace the original memory. The aim of this proposal is to advance our understanding of this fundamental type of memory updating that results in the swapping of one memory by another. To achieve this, we will exploit the advantages offered by the relatively simple brain and behaviour of the mollusc Lymnaea. While having a CNS of only ~20,000 neurons, this animal nevertheless shares all of the basic features of associative memory formation displayed by far more complex animals, including humans. This allows us to study a universal form of behavioural adaptation and flexibility at a level of cellular and molecular detail that would not be possible in more complex animals. Because we know that the process of memory formation and its underlying neural and molecular mechanisms are evolutionarily highly conserved, this research is likely to reveal principles and mechanisms of behavioural flexibility that apply equally to both simple and complex animals.In the longer term this research may lead to the discovery of new drugs or procedures that can modify the flexibility of memory formation including the potential benefit that this may have for the treatment of memory disorders including post-traumatic stress disoder (PTSD). In PTSD the memory of a traumatic event becomes very strong and almost unsusceptible to interference. All the attempts to supress this memory have targeted the reconsolidation process that can be evoked long time after the stressful experience when the memory has already been stored for the long-term. Our work on memory blocking and replacement during the process of consolidation, may offer alternative opportunities for fundamental research in this clinical area.