D1Dopamine Receptor dDA1 Is Required in the Mushroom Body Neurons for Aversive and Appetitive Learning inDrosophila

Abstract

Drosophilahas robust behavioral plasticity to avoid or prefer the odor that predicts punishment or food reward, respectively. Both types of plasticity are mediated by the mushroom body (MB) neurons in the brain, in which various signaling molecules play crucial roles. However, important yet unresolved molecules are the receptors that initiate aversive or appetitive learning cascades in the MB. We have shown previously that D₁dopamine receptor dDA1 is highly enriched in the MB neuropil. Here, we demonstrate that dDA1 is a key receptor that mediates both aversive and appetitive learning in pavlovian olfactory conditioning. We identified two mutants,dumb¹anddumb², with abnormal dDA1 expression. When trained with the same conditioned stimuli, bothdumballeles showed negligible learning in electric shock-mediated conditioning while they exhibited moderately impaired learning in sugar-mediated conditioning. These phenotypes were not attributable to anomalous sensory modalities ofdumbmutants because their olfactory acuity, shock reactivity, and sugar preference were comparable to those of control lines. Remarkably, thedumbmutant's impaired performance in both paradigms was fully rescued by reinstating dDA1 expression in the same subset of MB neurons, indicating the critical roles of the MB dDA1 in aversive as well as appetitive learning. Previous studies using dopamine receptor antagonists implicate the involvement of D₁/D₅receptors in various pavlovian conditioning tasks in mammals; however, these have not been supported by the studies of D₁- or D₅-deficient animals. The findings described here unambiguously clarify the critical roles of D₁dopamine receptor in aversive and appetitive pavlovian conditioning.