Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3-and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition.Studies in higher primates and humans have led to the idea that the hippocampus is required for different types of memory, such as declarative (Squire 1992) or episodic memory (Tulving 1983). Independently of the type of memory, the hippocampus might be engaged in different memory processes, such as encoding, consolidation, and retrieval. Lesion studies in animals provide further support for the transient requirement of the hippocampus in the process of long-term memory formation Anagnostaras et al. 1999) in agreement with the theory of Squire (1992), describing the hippocampus as a temporary memory buffer that enlists the prefrontal cortex, where the information is ultimately stored.The hippocampal structure is functionally heterogeneous, with different portions of the longitudinal axis having different functional roles, certainly due to differences in connectivity (Moser and Moser 1998). Indeed, the dorsal hippocampus seems to be highly involved in spatial learning (Moser et al. 1993(Moser et al. , 1995, which is consistent with the major visuo-spatial inputs received from the temporal and parietal cortices, whereas the ventral hippocampus presents a strong connectivity with both the hypothalamus and the amygdala, which potentially accounts for some effects of the hippocampal lesion on emotionality (Kjelstrup et al. 2002). Moreover, all hippocampal subregions are highly interconnected, and their arrangement suggests that, individually, they may su...

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.

Oxidative stress is one of the factors involved in age-related impairment of cardiac function. In the present study, we investigated the role of the catecholamine-degrading enzyme monoamine oxidase (MAO) in H(2)O(2) production in the hearts of young, adult, and old rats. MAO-dependent H(2)O(2) production, measured by a chemiluminescence-based assay, increased with age, reaching the maximum in 24-mo-old rats (7.5-fold increase vs. 1-mo-old rats). The following observations indicate that the age-dependent increase in H(2)O(2) generation was fully related to the MAO-A isoform: 1) at all the ages tested, chemiluminescence production was inhibited by the MAO-A inhibitor clorgyline but not by the MAO-B inhibitor RO-19 6327; 2) enzyme assay, Western blot, and semiquantitative RT-PCR analysis showed an age-dependent increase in cardiac MAO-A activity, immunodetection, and mRNA expression, respectively; and 3) the MAO-B isoform was undetectable by enzyme assay and Western blot analysis. These results suggest that MAO-A could be a major source of H(2)O(2) in the aging heart.

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