Neuromodulation of flexible foraging

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'Should I stay or should I go?' is a type of decision that we all repeatedly face. How animals solve this type of dilemma has been of interest across a wide range of disciplines, including psychology, economics, artificial intelligence and behavioural ecology. Strikingly, a well-established efficient solution to the problem emerged from studying animal foraging behaviour: an animal should only continue to persist with its current strategy if it yields greater returns than the average of the opportunities available elsewhere in the environment. This framework, called the Marginal Value Theorem (MVT), has proven remarkably effective in explaining stay-or-leave decisions across a wide variety of settings and animal species, from foraging for food in invertebrates to searching for information in humans. Nonetheless, it is not clear how the brain keeps track of the key variables to enable this to happen efficiently.In neuroscience, it is generally accepted that brain chemicals such as dopamine and serotonin play essential roles in coordinating adaptive behaviour. For example, disrupting these chemicals, either experimentally using pharmacological agents, through natural processes in healthy ageing, or as a consequence of psychiatric or neurological disease, can change how quickly animals adapt to changes in their environment. Importantly, our understanding of these chemicals' roles comes mainly from simple decision making tasks where animals make repeated choices between options and update their behaviour based on trial-and-error experience. Therefore, a major gap in our knowledge is the roles these chemicals play in guiding more naturalistic dynamic foraging decisions.Intriguingly, some of our team's recent work has demonstrated that dopamine can simultaneously signal two different variables that could be important for such foraging decisions: (1) transient fluctuations in dopamine (lasting <1 second) that track the difference between the expected and obtained reward, believed to be an essential teaching signal for learning reward values, and (2) sustained changes in dopamine (lasting multiple seconds and longer) that track the average potential gains in the environment. Moreover, recent methodological advances have revolutionised our ability to monitor moment-by-moment changes in brain chemicals as well as to manipulate them with sub-second precision.These two developments set the stage for us to address for the first time what role dopamine, in concert with serotonin, plays in implementing efficient dynamic stay-or-leave decision making. First, we will measure dopamine levels in the brains of mice performing a foraging task using an optical technique called fibre photometry. By manipulating (i) how often they get rewards in the patch they are foraging in and (ii) how long it will take them to reach an alternative foraging site, we can determine how moment-by-moment changes in dopamine correlate with their decisions to stay or leave and how these align with predictions from models.Second, we will test whether these changes in dopamine play a causal role in animals' choices to stay or leave. To do this, we will use a technique called optogenetics to selectively turn on or off neurons that express dopamine as the mice perform the foraging task.Third, we will investigate whether another brain chemical, serotonin, influences stay-or-leave foraging decisions by modulating dopamine release. To do this, we will use new combinations of techniques to manipulate serotonin while simultaneously monitoring dopamine as mice perform the foraging task, using the same techniques as described above. We will test our hypothesis that boosting serotonin promotes persistence by modulating dopamine release in response to rewards.Together, this will provide important insights into how dopamine interacts with serotonin to enable efficient flexibility in naturalistic environments.