An Octopamine-Mushroom Body Circuit Modulates the Formation of Anesthesia-Resistant Memory in Drosophila

Background: Drosophila olfactory aversive conditioning produces two components of intermediate-term memory: anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM). Recently, the anterior paired lateral (APL) neuron innervating the whole mushroom body (MB) has been shown to modulate ASM via gap-junctional communication in olfactory conditioning. Octopamine (OA), an invertebrate analog of norepinephrine, is involved in appetitive conditioning, but its role in aversive memory remains uncertain. Results: Here, we show that chemical neurotransmission from the APL neuron, after conditioning but before testing, is necessary for aversive ARM formation. The APL neurons are tyramine, T beta h, and OA immunopositive. An adult-stage-specific RNAi knockdown of T beta h in the APL neurons or Oct beta 2R OA receptors in the MB alpha'beta' Kenyon cells (KCs) impaired ARM. Importantly, an additive ARM deficit occurred when T beta h knockdown in the APL neurons was in the radish mutant flies or in the wild-type flies with inhibited serotonin synthesis. Conclusions: OA released from the APL neurons acts on alpha'beta' KCs via Oct beta 2R receptor to modulate Drosophila ARM formation. Additive effects suggest that two parallel ARM pathways, serotoninergic DPM-alpha beta KCs and octopaminergic APL-alpha'beta' KCs, exist in the MB.