Abstract
Accumulating evidence suggests a critical role for epigenetic regulations in long term memory (LTM) formation. Among them, post-translational modifications of proteins, as histone acetylation, are an important regulator of chromatin remodelling and gene transcription. While the implication of histone acetylation in memory consolidation is widely accepted, less is known about its role in memory reconsolidation i.e. during memory restabilization after its reactivation. In the present study, we investigated the role of histone acetylation during the initial consolidation and the reconsolidation of spatial memory, using a weak massed learning procedure in the Morris water maze paradigm in mice. Usually a weak learning is sufficient for short term memory (STM) formation, but insufficient to upgrade STM to LTM. We found that promoting histone acetylation through intra-hippocampal infusion of a class I selective histone deacetylase (HDAC) inhibitor immediately after a subthreshold spatial learning improved LTM but not STM retention. More importantly, inhibiting HDAC activity after the reactivation of a weak memory promoted specifically LTM reconsolidation without affecting post-reactivation STM. These findings argue in favour of an important role for histone acetylation in memory consolidation, and more particularly during the reconsolidation of spatial memory in mice.
Highlights
Class I (HDAC 1, 2, 3 and 8) specific HDAC inhibitor sodium butyrate (NaB) rescued fear memory deficits in rodents[23,24] and treatment with other HDAC inhibitors enhanced memory reconsolidation[20,25]
We chose the allocentric version of the Morris water maze task (MWM), in which animals have to create a viewpoint-independent representation incorporating distal cues, in order to compute the location of the platform using this cognitive map of the environment
In this study we report that inhibiting HDAC activity into the dorsal hippocampus after a subthreshold spatial learning task promoted the consolidation and reconsolidation of Long term memory (LTM), without affecting post-training and post-reactivation short term memory (STM) processes
Summary
Class I (HDAC 1, 2, 3 and 8) specific HDAC inhibitor sodium butyrate (NaB) rescued fear memory deficits in rodents[23,24] and treatment with other HDAC inhibitors enhanced memory reconsolidation[20,25]. Most of studies are focused on the role of epigenetic mechanisms on the reconsolidation phase of aversive memories depending on the amygdala in simple tasks as the fear conditioning[20,23,25] These tasks require aversive reinforcement, i.e. an electric shock, and numerous studies have shown the importance of epigenetic mechanisms in stress[26]. It seemed to us important to investigate the role of epigenetic regulations in a less stressful and more complex memory task than an aversive Pavlovian conditioning In this present study, we investigated the role of histone acetylation during initial consolidation but especially during reconsolidation in a cognitive learning task dependent on the hippocampal formation. We tested the impact of an intra-hippocampal infusion of a class I specific HDAC inhibitor, immediately after a weak learning experience or after reactivation of a spatial memory trace in MWM paradigm
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