Abstract

Memory liberates us from the present and plays a major role in guiding appropriate behavioural responses to the challenges posed by a complex and uncertain world. Research over many years has shown that, at the psychological level, memories are flexible and can be moulded so that they are more or less able to control our behaviour. Our studies in rats of hippocampal-dependent contextual fear conditioning, perhaps the simplest form of Pavlovian learning and memory, have shown that brief reexposure to the training context causes fear memory reconsolidation, whereas prolong exposure induces memory extinction. The mechanisms that control whether memory will reconsolidate or extinguish are very poorly understood. Our current work indicates that the activity of three plasticity-associated molecules in the hippocampus, Zif268, brain-derived neurotrophic factor and Arc, determine whether reconsolidation or extinction prevails. In addition, the differential activities induced by brief versus prolonged context exposure describe a gate for post-retrieval memory processes. Characterising the molecular and cellular mechanisms underlying the reconsolidation and extinction of long-term memory, and discerning the precise conditions of recall that engage distinct cellular mechanisms has potential importance to the development of therapeutic strategies for memory disorders.