How hunger influences aversive learning in fruit flies

It has been shown that the internal states that animals experience when they are thirsty, hungry, sleepy, or aggressive are related to the combined activity of various neuromodulators and neurotransmitters. These chemical messengers can dramatically alter the excitability and functional connectivity of neurons, which in turn plays a role in shaping animal behavior.

Previous studies on drosophila (small fruit flies) have shown that energy homeostasis in these insects is regulated by various neurohormones/modulators, which have different impacts on their physiology and behavior. These include insulin-like peptides (dILPs) and adipokinetic hormone (AKH), ​​hormones with similar functions to insulin and glucagon in mammals, respectively.

Researchers from the Centre for Neural Circuits and Behaviour at the University of Oxford recently conducted a study into how these hunger-related neurohormones influence the learning of associations between stimuli and unpleasant or negative outcomes (i.e. aversive learning) in fruit flies. Their paper, published in Neuronshows that the hormone AKH plays a key role in modulating aversive reinforcement learning.

“Starving animals require compensatory mechanisms to maintain flexible brain function, while modulation reconfigures circuits to prioritize resource seeking,” wrote Eleonora Meschi, Lucille Duquenoy, and colleagues in their paper. “In Drosophila, hunger inhibits dopamine aversive reinforcement neurons (DANs) to allow expression of food-seeking memories. Multitasking the reinforcement system for motivation potentially compromises aversive learning.”

Aversion learning is an evolutionary process by which animals begin to associate specific stimuli with unpleasant outcomes, after repeated negative experiences following exposure to those stimuli. This often results in behaviors aimed at avoiding the stimulus and the experiences associated with it.

Fruit flies, for example, can be trained to associate specific odors with electric shocks or positive rewards (e.g., eating sugar or other nutrients). The researchers investigated whether hunger modulates the establishment of connections between an odor and electric shocks in the flies.

To do this, they deprived the flies of food for 24 hours and studied the effect of this practice on their aversion learning. The team then used various optogenetic techniques and in vivo imaging tools to better understand the role played by neurohormones in the observed effects.

“We found that chronic hunger modestly enhances aversion learning and that both satiation learning and hunger learning require endocrine adipokinetic hormone (AKH) signaling,” Meschi, Duquenoy, and colleagues wrote. “Circulating AKH influences aversion learning via its receptor in four ventral brain neurons, two of which are octopaminergic.”

The researchers’ experiments revealed that AKH, the fly equivalent of glucagon, sets baseline and hunger-reinforced aversive learning levels by acting through specific neurons that release the neurotransmitter octopamine. This neurotransmitter modulates inputs to dopamine neurons involved in aversive reinforcement learning.

“Connectomics revealed that AKH receptor-expressing neurons are upstream of multiple classes of ascending neurons, many of which are presynaptic to aversively reinforce DANs,” Meschi, Duquenov, and colleagues wrote.

“Octopaminergic modulation and output of at least one of these ascending pathways are required for aversive learning reinforced by shock and bitter taste. We propose that coordinated enhancement of input compensates for hunger-directed inhibition of aversive DANs to preserve reinforcement when needed.”

The results of this recent study contribute to a better understanding of how hunger affects aversive learning in fruit flies, particularly by highlighting the key role of the neurohormone AKH. In the future, it could inspire new research aimed at validating the patterns observed by the researchers in other animal models.

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