Dopamine neurons that inform Drosophila olfactory memory have distinct, acute functions driving attraction and aversion

PLoS Biol. 2024 Nov 18;22(11):e3002843. doi: 10.1371/journal.pbio.3002843. eCollection 2024 Nov.

Abstract

The brain must guide immediate responses to beneficial and harmful stimuli while simultaneously writing memories for future reference. While both immediate actions and reinforcement learning are instructed by dopamine, how dopaminergic systems maintain coherence between these 2 reward functions is unknown. Through optogenetic activation experiments, we showed that the dopamine neurons that inform olfactory memory in Drosophila have a distinct, parallel function driving attraction and aversion (valence). Sensory neurons required for olfactory memory were dispensable to dopaminergic valence. A broadly projecting set of dopaminergic cells had valence that was dependent on dopamine, glutamate, and octopamine. Similarly, a more restricted dopaminergic cluster with attractive valence was reliant on dopamine and glutamate; flies avoided opto-inhibition of this narrow subset, indicating the role of this cluster in controlling ongoing behavior. Dopamine valence was distinct from output-neuron opto-valence in locomotor pattern, strength, and polarity. Overall, our data suggest that dopamine's acute effect on valence provides a mechanism by which a dopaminergic system can coherently write memories to influence future responses while guiding immediate attraction and aversion.

MeSH terms

  • Animals
  • Avoidance Learning / physiology
  • Behavior, Animal / physiology
  • Dopamine* / metabolism
  • Dopaminergic Neurons* / metabolism
  • Dopaminergic Neurons* / physiology
  • Drosophila / physiology
  • Drosophila melanogaster / physiology
  • Glutamic Acid / metabolism
  • Memory* / physiology
  • Octopamine / metabolism
  • Optogenetics
  • Reward
  • Smell* / physiology

Substances

  • Dopamine
  • Octopamine
  • Glutamic Acid

Grants and funding

FM, YM, SO, XYZ, and ACC were supported by grants MOE-2013-T2-2-054, MOE2017-T2-1-089, and MOE2019-T2-1-133 from the Ministry of Education, Singapore; JCS and ACC were supported by grants 1231AFG030 and 1431AFG120 from the A*STAR Joint Council Office. YM was supported by Duke-NUS Medical School and by a President’s Graduate Fellowship funded through the Jasmine Scholarship; JH was supported by the A*STAR Scientific Scholars Fund; SO was supported by a Khoo Postdoctoral Fellowship Award and an NMRC Young Investigator Research Grant; XYZ was supported by a Yong Loo Lin School of Medicine scholarship. The authors were supported by a Biomedical Research Council block grant to the Institute of Molecular and Cell Biology, and a Duke-NUS Medical School grant to ACC. https://www.nmrc.gov.sg/https://www.moe.gov.sg/https://medicine.nus.edu.sg/https://www.duke-nus.edu.sg/https://www.a-star.edu.sg/imcbhttps://www.a-star.edu.sg/Research/bmrc The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.