Abstract

DNA methyltransferases (Dnmts) - epigenetic writers catalyzing the transfer of methyl-groups to cytosine (DNA methylation) – regulate different aspects of memory formation in many animal species. In honeybees, Dnmt activity is required to adjust the specificity of olfactory reward memories and bees’ relearning capability. The physiological relevance of Dnmt-mediated DNA methylation in neural networks, however, remains unknown. Here, we investigated how Dnmt activity impacts neuroplasticity in the bees’ primary olfactory center, the antennal lobe (AL) an equivalent of the vertebrate olfactory bulb. The AL is crucial for odor discrimination, an indispensable process in forming specific odor memories. Using pharmacological inhibition, we demonstrate that Dnmt activity influences neural network properties during memory formation in vivo. We show that Dnmt activity promotes fast odor pattern separation in trained bees. Furthermore, Dnmt activity during memory formation increases both the number of responding glomeruli and the response magnitude to a novel odor. These data suggest that Dnmt activity is necessary for a form of homoeostatic network control which might involve inhibitory interneurons in the AL network.

Highlights

  • Learning reduces global DNA methylation in the honeybee brain and affects the expression of memory-associated genes[19]

  • We hypothesized that Dnmts mediate learning-related plasticity in the honeybee primary olfactory center and strengthen stimulus-specific memory formation in this neuropil

  • We combined the use of a non-specific Dnmt inhibitor, RG10824–26, with in vivo Ca2+-imaging of the AL output neurons

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Summary

Introduction

Learning reduces global DNA methylation in the honeybee brain and affects the expression of memory-associated genes[19]. Dnmt inhibition impaired odor response pattern separation between a trained and a new odor. The overall number of glomeruli responsive to a new odor and their response strength was reduced after Dnmt inhibition. Inhibiting Dnmts did not change the response to the learned odor. These results suggest that Dnmts are involved in regulating plasticity in the inhibitory neural network of the AL during memory formation

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