Selective suppression and recall of long-term memories in Drosophila.

Dominique Siegenthaler,Vanessa Bräuler,Jan Pielage,Benjamin Escribano,Josh Dubnau

doi:10.1371/journal.pbio.3000400

Dominique Siegenthaler, Vanessa Bräuler + Show 3 more

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https://doi.org/10.1371/journal.pbio.3000400

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Journal: PLoS Biology	Publication Date: Aug 27, 2019
Citations: 10	License type: CC BY 4.0

Affiliation: University of Kaiserslautern

Abstract

Adaptive decision-making depends on the formation of novel memories. In Drosophila, the mushroom body (MB) is the site of associative olfactory long-term memory (LTM) storage. However, due to the sparse and stochastic representation of olfactory information in Kenyon cells (KCs), genetic access to individual LTMs remains elusive. Here, we develop a cAMP response element (CRE)-activity–dependent memory engram label (CAMEL) tool that genetically tags KCs responding to the conditioned stimulus (CS). CAMEL activity depends on protein-synthesis–dependent aversive LTM conditioning and reflects the time course of CRE binding protein 2 (CREB2) activity during natural memory formation. We demonstrate that inhibition of LTM-induced CAMEL neurons reduces memory expression and that artificial optogenetic reactivation is sufficient to evoke aversive behavior phenocopying memory recall. Together, our data are consistent with CAMEL neurons marking a subset of engram KCs encoding individual memories. This study provides new insights into memory circuitry organization and an entry point towards cellular and molecular understanding of LTM storage.

Highlights

Successful adaptation to aversive stimuli through the formation of associative memories is essential for the survival of most animals
To enable specific labeling and manipulation of olfactory long-term memory (LTM)-encoding Kenyon cell (KC), we developed a CREB reporter tool based on the split-Gal4 system
We observed a significant increase in cAMP response element (CRE)-activity–dependent memory engram label (CAMEL)

Summary

Introduction

Successful adaptation to aversive stimuli through the formation of associative memories is essential for the survival of most animals. Drosophila aversive olfactory conditioning has been successfully used in the past to unravel the molecular mechanisms underlying long-term associative memory [4,5,6,7]. The mushroom body (MB), the site of associative olfactory learning in insects, consists of 7 types (αβc, αβs, αβp, α’β’m, α’β’ap, γm, and γd) of Kenyon cells (KCs) that project into specific layers in the α/β, α’/β’, and γ MB lobes that represent functional domains dedicated to different aspects of memory acquisition, storage, and retrieval [8,9,10,11,12,13,14,15,16,17,18,19].

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