Abstract
BackgroundAnimals’ capacities for different forms of learning do not mature simultaneously during ontogenesis but the molecular mechanisms behind the delayed development of specific types of memory are not fully understood. Mollusks are considered to be among the best models to study memory formation at the molecular level. Chromatin remodeling in developmental processes, as well as in long-term memory formation, was recently shown to play a major role. Histone acetylation is a key process in the chromatin remodeling and is regulated through the signaling cascades, for example MAPK/ERK. Previously, we found that MAPK/ERK is a key pathway in the formation of the food aversion reflex in Helix. Pretreatment with upstream ERK kinase inhibitor PD98059 prevented food avoidance learning in adult Helix. In contrast to adult snails, juveniles possess immature plasticity mechanisms of the avoidance reflex until the age of 2–3 months while the MAPK/ERK cascade is not activated after aversive learning. In the present study, we focused on the potential MAPK/ERK target - histone H3.Methodology/Principal FindingsHere we found that a significant increase in histone H3 acetylation occurs in adult animals after learning, whereas no corresponding increase was observed in juveniles. The acetylation of histone H3 is regulated by ERK kinase, since the upstream ERK kinase inhibitor PD98059 prevented the increase of histone H3 acetylation upon learning. We found that the injection of histone deacetylase inhibitor sodium butyrate (NaB) prior to training led to induction in histone H3 acetylation and significantly ameliorated long-term memory formation in juvenile snails.Conclusions/SignificanceThus, MAPK/ERK-dependent histone H3 acetylation plays an essential role in the formation of food aversion in Helix. Dysfunction of the MAPK/ERK dependent histone H3 acetylation might determine the deficiency of avoidance behavior and long-term plasticity in juvenile animals. Stimulation of histone H3 acetylation in juvenile animals by NaB promoted avoidance plasticity.
Highlights
Despite extensive research on molecular mechanisms of formation, consolidation and retention of memory traces in the brain, the major phenomena in neurobiology, i.e. learning and memory, are poorly understood
We found that the injection of NaB stimulates histone H3 acetylation in the subesophageal complex of ganglia of trained juvenile snails (Fig. 2B)
We found a significant activation of MAPK/ERK in the subesophageal complex of ganglia of the adult snails after formation of food aversion learning, which was abolished by a pretreatment with MEK (ERK upstream kinase) inhibitor PD98059 [13]
Summary
Despite extensive research on molecular mechanisms of formation, consolidation and retention of memory traces in the brain, the major phenomena in neurobiology, i.e. learning and memory, are poorly understood. It has been shown that long-term memory formation is determined by a rearrangement of neuronal networks and by an increase in efficiency of synaptic contacts between neurons These processes require modulation of the genome [1,2,3,4,5]. It was recently shown that epigenetic remodeling is involved in learning and memory, in the same way as in cellular differentiation and development [5]. It is well-known that animals capacities for different forms of learning do not mature simultaneously during ontogenesis. Animals’ capacities for different forms of learning do not mature simultaneously during ontogenesis but the molecular mechanisms behind the delayed development of specific types of memory are not fully understood. We focused on the potential MAPK/ERK target - histone H3
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