Concerted Actions of Octopamine and Dopamine Receptors Drive Olfactory Learning

Aminergic signaling modulates associative learning and memory. Substantial advance has been made in Drosophila on the dopamine receptors and circuits mediating olfactory learning; however, our knowledge of other aminergic modulation lags behind. To address this knowledge gap, we investigated the role of octopamine in olfactory conditioning. Here, we report that octopamine activity through the beta-adrenergic-like receptor Oct beta 1R drives aversive and appetitive learning: Oct beta 1R in the mushroom body alpha beta neurons processes aversive learning, whereas Oct beta 1R in the projection neurons mediates appetitive learning. Our genetic interaction and imaging studies pinpoint cAMP signaling as a key downstream effector for Oct beta 1R function. The rutabaga-adenylyl cyclase synthesizes cAMP in a Ca2+/calmodulin-dependent manner, serving as a coincidence detector for associative learning and likely representing a downstream target for Oct beta 1R. Supporting this notion, the double heterozygous rutabaga/+;oct beta 1r/+ flies perform poorly in both aversive and appetitive conditioning, while individual heterozygous rutabaga/+ and oct beta 1r/+ flies behave like the wild-type control. Consistently, the mushroom body and projection neurons in the oct beta 1r brain exhibit blunted responses to octopamine when cAMP levels are monitored through the cAMP sensor. We previously demonstrated the pivotal functions of the D-1 receptor dDA1 in aversive and appetitive learning, and the alpha 1 adrenergic-like receptor OAMB in appetitive learning. As expected, oct beta 1r genetically interacts with dumb (dDA1 mutant) in aversive and appetitive learning, but it interacts with oamb only in appetitive learning. This study uncovers the indispensable contributions of dopamine and octopamine signaling to aversive and appetitive learning. All experiments were performed on mixed sex unless otherwise noted.