DeMARRe · Risk and resilience in adolescent decision-making

Adolescents take more risks than adults do, contributing to the conventional framing of this period as one of great vulnerability. Surprisingly however, teenagers who engage in some degree of risk-taking exhibit more favorable psychosocial trajectories compared to those who avoid risks. This raises the intriguing possibility that taking risks during adolescence may, in fact, have enduring positive effects on adult behavior. The core objective of this proposal is to unravel the neural basis of how taking risks during adolescence can drive behavioral and neural circuit adaptations that promote resilience in adulthood. Risk-taking behavior can be studied in the context of decision making, where adolescents are more likely to explore risky choices, such as those with an uncertain outcome, than adults are. Strategy implementation under uncertainty conditions in adults is highly individualistic and is linked to activity in the dopamine system. As dopamine circuits develop during adolescence in a sex-specific manner, their maturation may contribute not only to the reduction in risk-taking observed between adolescence and adulthood, but also to sex differences in how risk modulates decision-making strategy. Finally, dopamine circuits may carry a neural imprint of the enduring positive effects on adult behavior. Here, I propose a concerted, multilevel experimental approach that builds from longitudinal behavioral and computational analyses of individualistic mouse decision-making across postnatal life in male and female mice. Embedding this core framework within sophisticated activity-mapping and network-manipulation techniques will allow me to dissect changes in dopaminergic networks during the transition from adolescence to adulthood that underlie decision-making strategy refinement, and to investigate whether this network refinement facilitates cognitive processes in adults, and, in turn, confers resilience against drug-taking and stress.