Abstract

Multiple spaced trials of aversive differential conditioning can produce two independent long-term memories (LTMs) of opposite valence. One is an aversive memory for avoiding the conditioned stimulus (CS+), and the other is a safety memory for approaching the non-conditioned stimulus (CS-). Here, we show that a single trial of aversive differential conditioning yields one merged LTM (mLTM) for avoiding both CS+ and CS-. Such mLTM can be detected after sequential exposures to the shock-paired CS+ and -unpaired CS-, and be retrieved by either CS+ or CS-. The formation of mLTM relies on triggering aversive-reinforcing dopaminergic neurons and subsequent new protein synthesis. Expressing mLTM involves αβ Kenyon cells and corresponding approach-directing mushroom body output neurons, in which similar-amplitude long-term depression of responses to CS+ and CS- seems to signal the mLTM. Our results suggest that animals can develop distinct strategies for occasional and repeated threatening experiences.

Highlights

  • To survive in a complex environment, animals need to learn from threatening experiences to avoid potential dangers

  • Consistent with previous reports (Davis and Zhong, 2017; Shuai et al, 2010; Tully et al, 1994), flies exposed to single-trial conditioning rapidly lost their ability to discriminate CS+ and CS– within 1 day

  • Testing CS+ or CS– versus Air revealed traininginduced long-lasting avoidances of CS+ and CS– (Figure 1-figure supplement 2). We wondered whether such aversive long-term memories (LTMs) require new protein synthesis to consolidate

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Summary

Introduction

To survive in a complex environment, animals need to learn from threatening experiences to avoid potential dangers. After repetitive spaced trials of conditioning, animals form two complementary long-term memories (LTMs) of opposite valence (Jacob and Waddell, 2020; Pollak et al, 2008; Pollak et al, 2010), including the aversive memory to the conditioned stimulus (CS+) and the rewarding memory to the non-conditioned stimulus (CS–) (Figure 1-figure supplement 1). Such complementary LTMs result in enhanced long-lasting discrimination between CS+ and CS– through guiding avoidance to CS+ and approach to CS–.

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