Contrasting Effects of Histone Deacetylase Inhibitors on Reward and Aversive Olfactory Memories in the Honey Bee.

Gabrielle Lockett,Paul Helliwell,Fiona Wilkes,Ryszard Maleszka

doi:10.3390/insects5020377

Abstract

Much of what we have learnt from rodent models about the essential role of epigenetic processes in brain plasticity has made use of aversive learning, yet the role of histone acetylation in aversive memory in the honey bee, a popular invertebrate model for both memory and epigenetics, was previously unknown. We examined the effects of histone deacetylase (HDAC) inhibition on both aversive and reward olfactory associative learning in a discrimination proboscis extension reflex (PER) assay. We report that treatment with the HDAC inhibitors APHA compound 8 (C8), phenylbutyrate (PB) or sodium butyrate (NaB) impaired discrimination memory due to impairment of aversive memory in a dose-dependent manner, while simultaneously having no effect on reward memory. Treatment with C8 1 h before training, 1 h after training or 1 h before testing, impaired aversive but not reward memory at test. C8 treatment 1 h before training also improved aversive but not reward learning during training. PB treatment only impaired aversive memory at test when administered 1 h after training, suggesting an effect on memory consolidation specifically. Specific impairment of aversive memory (but not reward memory) by HDAC inhibiting compounds was robust, reproducible, occurred following treatment with three drugs targeting the same mechanism, and is likely to be genuinely due to alterations to memory as sucrose sensitivity and locomotion were unaffected by HDAC inhibitor treatment. This pharmacological dissection of memory highlights the involvement of histone acetylation in aversive memory in the honey bee, and expands our knowledge of epigenetic control of neural plasticity in invertebrates.

Highlights

Epigenetic control systems such as DNA methylation and post-translational histone modifications have the capacity to control the organism’s gene expression potential without changing the underlyingDNA sequence
We previously showed that DNA methylation is involved in memory processing in the honey bee [4] suggesting that the function of this epigenetic process in neural plasticity is phylogenetically conserved [2,5,6]
To our knowledge this is the first assessment of the role of histone acetylation in aversive memory in the honey bee, and it uncovered a striking contrast with reward memory, which was unaffected by treatment with histone deacetylase (HDAC) inhibitors

Summary

Introduction

Epigenetic control systems such as DNA methylation and post-translational histone modifications have the capacity to control the organism’s gene expression potential without changing the underlyingDNA sequence. Epigenetic control systems such as DNA methylation and post-translational histone modifications have the capacity to control the organism’s gene expression potential without changing the underlying. We previously showed that DNA methylation is involved in memory processing in the honey bee [4] suggesting that the function of this epigenetic process in neural plasticity is phylogenetically conserved [2,5,6]. Regulation of chromatin structure through post-translational modification of histone proteins, primarily histone H3 phosphorylation and acetylation, is an important early step in the induction of synaptic plasticity and formation of long-term memory. Histone acetylation was first shown to have a role in memory in Aplysia [7], and training in the crab alters histone acetylation in the central brain [8]

Results

Discussion

Conclusion