The formation of long-term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin-proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis-dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation.

From insects to humans, successful navigation relies on retained representations of spatial relations. These representations are thought to depend on the hippocampal formation, particularly those that are independent of the navigator (allocentric representations). The Morris water maze is a simple and popular task often used to assess spatial navigation. But how animals navigate toward and retain information regarding the location of the goal in this task remains unclear. We provide a comprehensive account of how the water maze is accomplished behaviourally. Our findings suggest that animals solve the task using distal cues via an initial view-matching strategy that is supported by egocentric guidance. Through increased training, however, an emergence of an egocentric-guiding strategy combined with the animal's greater ability to infer the hidden platform's location (via allocentric extrapolation) emerges. We also demonstrate that behavioural changes, towards a more allocentric strategy, are reflected in increases in hippocampal brain-derived neurotrophic factor.

Research has focused mainly on the acquisition phase of spatial tasks, while retention has been relatively ignored. In three experiments, we determine the type of information that is retained in spatial memory using the water maze task. In experiment 1, we demonstrate that by rotating the distal cues 180 degrees post-acquisition Wistar rats search in the opposite area to where the platform should be. This search continues for a maximum of 30 s. We then demonstrate (experiment 2) that by rotating the starting position (180 degrees post-acquisition) animals remain at the starting-point for 10 s. They then commence searching in the platform area. In experiment 3, we demonstrate that rotations of distal cues and starting position post-acquisition impair retention of the platform's location. We suggest that the association between the configuration of distal cues and platform location is retained in memory but the association is fragile and sensitive to disruption.

Spatial learning in the water maze is thought to rely both on distal cues and vestibular information [Aggleton JP, Vann SD, Oswald CJP, Good M. Identifying cortical inputs to the rat hippocampus that subserves allocentric spatial processes: a simple problem with a complex answer. Hippocampus 2000;10:466-74; Pearce JM. Animal learning and cognition: an introduction. UK: Psychology Press; 1997]. Experiment 1 demonstrates that while water maze retention relies primarily on cue-platform based associations, this strategy is not precise, as animals tend to focus at the side of the pool. In experiment 2, we demonstrate that vestibular rotation eliminates this inaccuracy. These experiments highlight the importance of both cue and vestibular information for accurate retention of the water maze.

Hippocampal protein synthesis is dependent upon a number of different molecular and cellular mechanisms that act together to make previously labile memories more stable and resistant to disruption. Both brain-derived neurotrophic factor (BDNF) and extracellular signal-Regulated kinase (ERK) are known to play an important role in protein synthesis-dependent memory consolidation, via the mitogen-activated protein-kinase (MAP-K) signaling pathway during the transcription phase of protein synthesis. The current study investigates the influence of protein synthesis inhibition (PSI) by cycloheximide on spatial learning and memory. In an initial experiment, the authors utilized two doses of cycloheximide (0.5 mg/kg and 1.0 mg/kg, intraperitoneally) to determine the dose at which long-term (Ͼ24 hours) memories are impaired. A second experiment was designed to investigate the effect of PSI on the formation of cue-platform associations in the watermaze, and on BDNF and ERK expression in the hippocampus. At the higher dose (1.0 mg/kg) cycloheximide resulted in impaired retention of the water maze. BDNF and ERK expression was also down-regulated in animals injected with this dose of cycloheximide. Our results demonstrate a role of protein synthesis in spatial memory retention, along with a possible relationship between protein synthesis and hippocampal BDNF/ERK expression.