Abstract

Memory is created by several interlinked processes in the brain, some of which require long-term gene regulation. Epigenetic mechanisms are likely candidates for regulating memory-related genes. Among these, DNA methylation is known to be a long lasting genomic mark and may be involved in the establishment of long-term memory. Here we demonstrate that DNA methyltransferases, which induce and maintain DNA methylation, are involved in a particular aspect of associative long-term memory formation in honeybees, but are not required for short-term memory formation. While long-term memory strength itself was not affected by blocking DNA methyltransferases, odor specificity of the memory (memory discriminatory power) was. Conversely, perceptual discriminatory power was normal. These results suggest that different genetic pathways are involved in mediating the strength and discriminatory power of associative odor memories and provide, to our knowledge, the first indication that DNA methyltransferases are involved in stimulus-specific associative long-term memory formation.

Highlights

  • Epigenetic mechanisms, such as DNA methylation, are likely candidates for regulating genes involved in memory formation

  • Is DNA methylation differentially involved in short- versus longterm memory formation in insects similar to observations in mammals? And does DNA methylation affect the strength and discriminatory power of memory differently? To address these questions we investigated the effect of inhibiting DNA methyltransferases on associative olfactory learning and memory formation during classical conditioning in honeybees

  • We found that DNA methyltransferase inhibition did not affect learning during the conditioning procedure (Fig. 1A) or memory strength during the retrieval test (Fig. 1B) in any of the groups

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Summary

Introduction

Epigenetic mechanisms, such as DNA methylation, are likely candidates for regulating genes involved in memory formation. Recent studies in mammals [2,3,4,5,6,7,8,9] and honeybees [10] show that DNA methyltransferases are involved in long-term memory formation. Most of the studies done in mammals focused on the hippocampus region [2,3,4,6,8], some investigated DNA methylation in the amygdala [5,9] and cortex [7]. In the hippocampus and cortex there are dynamic changes in methylation patterns in single genes, e.g. in the memory-related factor bdnf, after learning [4,7,8]. Only distinct areas in the promoter and exon regions of single genes could be tested so far

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