Synaptic tagging and capture mechanisms during the formation of memory: an exploratory study
Silva, Bruno Teixeira da
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In everybody’s lives, there are strong emotional or surprising events that, for being special, are vividly remembered for a lifetime. Sometimes, these memories include one-shot images or details of associated daily life events that, for being ordinary, should have been rapidly forgotten. Why and how does the brain form and retain detailed memories of trivial events? The synaptic tagging and capture (STC) hypothesis of memory formation (Frey & Morris, Nature 1997) provides a theoretical framework that might explain the formation of these flashbulb memories at a cellular level. The hypothesis suggests that strong events, producing long-lasting memories, might stabilise memory for weak events by up-regulating the synthesis of late-phase plasticity-related proteins in neurons encoding memory traces for both events. This thesis tests this prediction of the STC hypothesis during the formation of long-term place memory in rodents. First, two new behavioural tasks are developed which provide sensitive measures of rapidly acquired place memory persistence - a new one-trial place memory task in the “event arena” and a modified delayed matching-to-place (DMP) protocol in the watermaze. Persistence of place memory is assessed and compared in these tasks. Given the important role of NMDA receptor activation during STC mechanisms, the contribution of NMDA and AMPA receptor activation in the hippocampus for the encoding and retrieval of place memory, respectively, is also established. Finally, weak and strong encoding events, leading to the formation of either shortor long-lasting place memory in the watermaze DMP task, are characterized. A second series of experiments investigates the possibility of synergistic interactions between different encoding events that occur in two different watermazes. First, weak and strong encoding events are arranged to occur within a short time-window to test behavioural analogues of the “strong-before-weak” and “weak-before-strong” STC paradigms characterised in electrophysiological experiments in rat hippocampal slices (Frey and Morris, 1997, 1998b). Then, after establishing i) the time course and local specificity of protein synthesis inhibition by intra-hippocampal infusion of anisomycin in vivo, ii) the dependence of long-term memory for strong encoding events on protein synthesis in the hippocampus, and iii) the induction of transcriptional and translational mechanisms in the hippocampus by strong encoding events, a behavioural analogue of the “strong-before-strong” STC paradigm (Frey and Morris, 1997) is also investigated. The results of these experiments are supportive of i) a role for hippocampal NMDA receptor-mediated synaptic plasticity in the encoding of rapidly acquired place memory; ii) a role for hippocampal AMPA receptor-mediated synaptic transmission in both encoding and retrieval of memory; and iii) a role for transcriptional and translational mechanisms in the hippocampus in the stabilisation of place memory. However, no evidence could be found supporting the involvement of synaptic tagging and capture mechanisms during the formation of long-lasting place memory.