Selective involvement of the lateral entorhinal cortex in the control of the olfactory memory trace during conditioned odor aversion in the rat

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Disconnection of the Entorhinal Cortex and Dorsomedial Striatum Impairs the Sensitivity to Instrumental Contingency Degradation

The capacity to detect changes in the causal efficacy of actions is mediated by a number of brain areas, including the entorhinal cortex (EC) and the posterior part of the dorsomedial striatum (pDMS). In this study we examined whether interactions between the EC and pDMS are required to detect changes in the instrumental contingency. Rats that received EC–pDMS disconnection lesions, that is, unilateral cell body lesions of the EC and contralateral dopamine depletions of the pDMS, were trained to press two levers, with one delivering food pellets and the other a sucrose solution. Thereafter, we tested whether rats were sensitive (1) to a selective devaluation of the value of one of two outcomes using a specific satiety procedure, and (2) to a selective degradation of one of two contingencies controlling instrumental choice behavior. Our results reveal that rats with EC–pDMS disconnection lesions were sensitive to outcome devaluation. However, unlike rats with sham lesions or unilateral EC and pDMS lesions, rats with EC–pDMS disconnection lesions showed a reduced sensitivity to contingency degradation. These findings suggest that EC and pDMS may be part of a neural system that supports the detection of changes in the causal relationship between an action and its consequences

Spatial Memory Consolidation is Associated with Induction of Several Lysine-Acetyltransferase (Histone Acetyltransferase) Expression Levels and H2B/H4 Acetylation-Dependent Transcriptional Events in the Rat Hippocampus

Numerous genetic studies have shown that the CREB-binding protein (CBP) is an essential component of long-term memory formation, through its histone acetyltransferase (HAT) function. E1A-binding protein p300 and p300/CBP-associated factor (PCAF) have also recently been involved in memory formation. By contrast, only a few studies have reported on acetylation modifications during memory formation, and it remains unclear as to how the system is regulated during this dynamic phase. We investigated acetylation-dependent events and the expression profiles of these HATs during a hippocampus-dependent task taxing spatial reference memory in the Morris water maze. We found a specific increase in H2B and H4 acetylation in the rat dorsal hippocampus, while spatial memory was being consolidated. This increase correlated with the degree of specific acetylated histones enrichment on some memory/plasticity-related gene promoters. Overall, a global increase in HAT activity was measured during this memory consolidation phase, together with a global increase of CBP, p300, and PCAF expression. Interestingly, these regulations were altered in a model of hippocampal denervation disrupting spatial memory consolidation, making it impossible for the hippocampus to recruit the CBP pathway (CBP regulation and acetylated-H2B-dependent transcription). CBP has long been thought to be present in limited concentrations in the cells. These results show, for the first time, that CBP, p300, and PCAF are dynamically modulated during the establishment of a spatial memory and are likely to contribute to the induction of a specific epigenetic tagging of the genome for hippocampus-dependent (spatial) memory consolidation. These findings suggest the use of HAT-activating molecules in new therapeutic strategies of pathological aging, Alzheimer's disease, and other neurodegenerative disorders