Modulation of cortical circuits and predictive neural coding by serotonin

Serotonin (5-HT) is a central neuromodulator implicated in the regulation of many processes and one of the most important targets for psychoactive drugs. It profoundly impacts decision-making and its dysregulation can contribute to altered perception as well as pathological conditions such as depression, anxiety or obsessive-compulsive disorders. Yet 5-HT’s function is not well understood, hence impeding progress towards better treatments. The broad aim of this work is to understand the involvement of 5-HT in decision-making under conditions of uncertainty. Uncertainty arises whenever partial, ambiguous, or contradictory information is present, a common occurrence in real-world situations. We propose that 5-HT neurons respond to increases in uncertainty caused by unexpected events. . Such effects are hypothesized to modulate behavior at various time-scales. At an immediate time-scale, 5-HT release may promote persistence into ongoing behaviors when outcomes are uncertain. At longer time scales, it may increase behavioral flexibility in response to changes in the environment. Mechanistically, the control exerted by 5HT over these process may be mediated by its ability to modulate the neural representation of prior expectations at different levels of the brain hierarchy. Additionally, to complement our study of 5-HT and uncertainty at the circuit and brain-wide level, we also investigate the inputs and outputs of 5-HT neurons that allow them to exert their behavioral effects.