MiR-12 and miR-124 contribute to defined early phases of long-lasting and transient memory

Julia Michely,Susanne Kraft,Uli Müller

doi:10.1038/s41598-017-08486-w

Abstract

MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in long-lasting synaptic plasticity and long-term memory (LTM). Since recent findings demonstrated a role of epigenetic regulation of gene expression in early memory phases we investigated whether epigenetic regulation by miRNAs also contributes to early memory phases. We used the olfactory associative learning paradigm in honeybees and addressed the contribution of miRNAs depending on the conditioning strength. We selected miR-12, miR-124, and miR-125 that have been implicated in processes of neuronal plasticity and analysed their contribution to non-associative and associative learning using miRNA inhibitors. Blocking miR-12, miR-124, or miR125 neither affects gustatory sensitivity nor habituation nor sensitization. Blocking the function of miR-12 and miR-124 during and shortly after 3-trial conditioning impairs different early memory phases. Although different, the function of miR-12 and miR-124 is also required for early phases of transient memory that is induced by 1-trial conditioning. Blocking miR-125 has no effect on early memory independent of the conditioning strength. These findings demonstrate that distinct miRNAs contribute to early phases of both, transient memories as well as long-lasting memories.

Highlights

MicroRNAs are important epigenetic regulators of mRNA translation implicated in longlasting synaptic plasticity and long-term memory (LTM)
All previous studies on the role of miRNA in associative learning focussed on long-term memory, leaving unclear whether miRNA function is required for early memory phases
Since miRNAs can potentially target different processes during the time course of learning and memory formation we injected the miRNA inhibitors either 4 h before or 1 h after conditioning. With this strategy we aim to identify the contribution of different miRNAs to early memory phases, a topic that has not been addressed so far

Summary

Introduction

MicroRNAs (miRNAs) are important epigenetic regulators of mRNA translation implicated in longlasting synaptic plasticity and long-term memory (LTM). Visual pattern learning likewise induces changes in the level of distinct miRNAs directly after conditioning[16], suggesting that in this organism learning triggers specific miRNA-mediated processes that contribute to memory formation This notion is substantiated by transient blocking of miR-932 and miR-210 by miRNA inhibitors before appetitive olfactory conditioning that impairs long-term memory in honeybees[17]. We recently showed that learning-induced histone modifications that are epigenetic regulators of gene expression modulate early memory phases in honeybees[18, 19] This prompted us to address the question whether miRNAs. Biosciences Zoology/Physiology-Neurobiology, ZHMB (Center of Human and Molecular Biology) Faculty NT – Natural Science and Technology, Saarland University, D-66123, Saarbrücken, Germany.

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