Solving conflicts: Modulation of choices and actions in the fly.

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Effective action-selection involves evaluating information from the outside world and our intrinsic needs to select the most appropriate action for each situation. Yet little is known about how external and internal cues are weighed and integrated in the brain to prioritise actions.This project investigates this fundamental biological problem using the fruit fly Drosophila, an excellent system to investigate the mechanistic basis of behaviour. We will build on our recent knowledge of the key neurons that mediate the choice between feeding and mating (Cheriyamkunnel et. al., Curr.Biol 2021) to characterise the mechanism that integrates modulatory signals to prioritise actions.Fruit flies have a brain of only 100,000 neurons, most of which have been mapped. Thanks to new genetic tools, single neurons can be manipulated and recorded in Drosophila with a level of temporal, spatial and genetic precision that is not available in any other model organism. With these tools, we can study how cues from the environment and from inside the animal are evaluated in brain circuits to select appropriate actions.The choice between food or sex is a pretty fundamental one - we have to eat to live and we have to reproduce to pass on our genes to the next generation. We have recently created an assay where food- and sex-deprived flies are confronted with the decision of whether to prioritise feeding or mating. These behaviours cannot be simultaneously displayed in flies, forcing the animal to make a decision and prioritise what to do. Crucially, we know a great deal about the neural basis of courtship and feeding behaviours. Thus, this assay is well suited to identify fundamental principles of action-selection that might apply to other behavioural conflicts and the brains of other organisms.We discovered that if a male fly is very hungry and sexually aroused, he will choose to eat over courting a female. However, the choice also depends on other factors like the quality of the food on offer and on how hungry and sex deprived the animal is. We found that the neurons that tell the fly to go and eat, or to go and mate are essentially competing with each other. If the need to eat is most urgent, the feeding neurons will take over; if the threat of starvation is less, then the urge to reproduce will win. Further, we found that the presence of a female makes the males eat faster, allowing them to move on to sex very quickly. These findings suggest that conflicting states (e.g. the urge to eat and to reproduce) do not always inhibit each other but may help each other. Our work provides the unique opportunity to understand how flies integrate sensory cues to make these behavioural choices, and ask what it reveals about the way the brain functions. In this project, we will identify the signals that convey hunger state, as well as the cues that broadcast the presence of a potential mate, to the action-selection centre in the brain. We will study how these signals are integrated in the neurons that steer the animal's actions, making each option more or less attractive. In objective 1, we will define how hunger signals are integrated in the brain to promote feeding over courtship. In objective 2, we will study how the motivation to mate makes the male eat faster, allowing him to quickly move to the female. In objective 3, we will reveal how males determine when to stop a given behaviour (e.g., feeding) to engage in another important task (e.g., mating). This action-selection is an example of the everyday conflicts animals need to solve but are difficult to tackle in mammals. By studying how the brain makes decisions at a molecular, cellular and circuit level, in a simpler system, we aim to reveal fundamental principles of action-selection that might be common to many species. This knowledge, in turn, will provide insight into how other more complex brains work, like our own.