Dopamine Receptor DAMB Signals via Gq to Mediate Forgetting in Drosophila

Cell Rep. 2017 Nov 21;21(8):2074-2081. doi: 10.1016/j.celrep.2017.10.108.


Prior studies have shown that aversive olfactory memory is acquired by dopamine acting on a specific receptor, dDA1, expressed by mushroom body neurons. Active forgetting is mediated by dopamine acting on another receptor, Damb, expressed by the same neurons. Surprisingly, prior studies have shown that both receptors stimulate cyclic AMP (cAMP) accumulation, presenting an enigma of how mushroom body neurons distinguish between acquisition and forgetting signals. Here, we surveyed the spectrum of G protein coupling of dDA1 and Damb, and we confirmed that both receptors can couple to Gs to stimulate cAMP synthesis. However, the Damb receptor uniquely activates Gq to mobilize Ca2+ signaling with greater efficiency and dopamine sensitivity. The knockdown of Gαq with RNAi in the mushroom bodies inhibits forgetting but has no effect on acquisition. Our findings identify a Damb/Gq-signaling pathway that stimulates forgetting and resolves the opposing effects of dopamine on acquisition and forgetting.

Keywords: dopamine receptors; memory acquisition; memory forgetting; mushroom body; olfactory learning.

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Conditioning, Classical / physiology
  • Cyclic AMP / metabolism
  • Dopamine / metabolism
  • Dopaminergic Neurons / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • Memory / physiology*
  • Mushroom Bodies / metabolism
  • Receptors, Dopamine / genetics
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D1 / genetics
  • Receptors, Dopamine D1 / metabolism*
  • Smell / physiology


  • Dop1R1 protein, Drosophila
  • Dop1R2 protein, Drosophila
  • Drosophila Proteins
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Cyclic AMP
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Dopamine