UCSF

Throughout the lifespan, the brain is sculpted by experience and by the developmental processes that prepare animals to face the challenges of each life stage. Adolescence and young adulthood represent critical times in which humans and other animals face the challenges associated with independence. During these times of exploration, specific learning experiences may shape neurodevelopmental trajectories and alter life outcomes. In Chapter 2, we focus on the idea that specific learning experiences in young adulthood may promote resilience in the face of environmental risk factors. We demonstrate that a cognitive training intervention in young adulthood can promote long-term resilience to cocaine-seeking behavior in mice. In Chapters 3 and 4, we shift to the role of developmental processes, particularly hormonal changes during puberty, in shaping frontal circuits and behaviors associated with these circuits. The frontal cortex matures during adolescence and is critical for the decision-making processes that shape life trajectories into adulthood. In Chapter 3, we show that pubertal hormones drive maturation of inhibitory neurotransmission in frontal cortex, which may have implications for the regulation of plasticity and learning across development. We also show that early exposure to pubertal hormones can induce an early reduction in flexible learning on a frontal cortex-dependent task, further supporting the idea that pubertal hormones may regulate developmental shifts in learning and decision-making. Chapter 4 extends these findings to affective behaviors, testing the role of pubertal hormones in the maturation of anxiety- and depression-related behavior, which both depend on interactions between frontal cortex and subcortical limbic structures. We find that gonadal hormones regulate anxiety-related behavior in a sex-specific manner during puberty in mice, while depression-related behavior increases with age regardless of gonadal hormone status. Our findings demonstrate that pubertal hormones regulate aspects of neural and behavioral maturation that may be critical for navigating this vulnerable life stage, indicating a need for further work on the implications of hormonal perturbation during puberty in humans. As we connect these results with the ideas presented in Chapter 2, we discuss adolescence as a critical time in which interventions may alter neurodevelopmental trajectories to promote emotional resilience and adaptive decision-making.