An octopamine-mushroom body circuit modulates the formation of anesthesia-resistant memory in Drosophila
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Updated: May 5, 2026

In Vivo Optical Calcium Imaging of Learning-Induced Synaptic Plasticity in Drosophila melanogaster
Published on: October 8, 2019
Chia-Lin Wu1, Meng-Fu Maxwell Shih, Pei-Tseng Lee
1Brain Research Center, National Tsing Hua University, Hsinchu 30013, Taiwan; Department of Biochemistry and Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan 333, Taiwan.
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, Tβh, and OA immunopositive. An adult-stage-specific RNAi knockdown of Tβh in the APL neurons or Octβ2R OA receptors in the MB α'β' Kenyon cells (KCs) impaired ARM. Importantly, an additive ARM deficit occurred when Tβh 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 α'β' KCs via Octβ2R receptor to modulate Drosophila ARM formation. Additive effects suggest that two parallel ARM pathways, serotoninergic DPM-αβ KCs and octopaminergic APL-α'β' KCs, exist in the MB.
Insights
Octopamine from Drosophila's APL neuron modulates aversive memory. This neurotransmitter acts on specific brain cells, revealing two parallel memory pathways in the mushroom body for anesthesia-resistant memory (ARM).
Area of Science:
- Neuroscience
- Animal Behavior
- Molecular Biology
Background:
- Drosophila olfactory conditioning forms anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM).
- Anterior paired lateral (APL) neurons modulate ASM via gap junctions.
- Octopamine (OA) is implicated in appetitive but not aversive memory.
Purpose of the Study:
- Investigate the role of the APL neuron and octopamine (OA) in Drosophila aversive memory.
- Determine the specific mechanisms by which OA influences aversive memory formation.
Main Methods:
- Utilized adult-stage-specific RNAi to knockdown tyramine beta-hydroxylase (Tβh) in APL neurons.
- Examined the impact of OA receptor (Octβ2R) knockdown in mushroom body Kenyon cells (KCs).
- Assessed memory deficits in genetically modified flies and under inhibited serotonin synthesis.
Main Results:
- APL neuron neurotransmission is crucial for aversive ARM formation.
- Knockdown of Tβh in APL neurons or Octβ2R in α'β' KCs impaired ARM.
- Additive memory deficits suggest parallel serotoninergic and octopaminergic pathways.
Conclusions:
- Octopamine (OA) from APL neurons acts on α'β' KCs via Octβ2R to modulate ARM.
- Two parallel pathways for ARM exist: serotoninergic (DPM-αβ KCs) and octopaminergic (APL-α'β' KCs).
- This study elucidates the neurochemical basis of aversive memory in Drosophila.

