Sex-correlated variability in exploration strategy in uncertain environments

Abstract

Every organism must balance between two goals: exploiting rewarding options when they are available and exploring more new information about potential better alternatives. Adaptively transition between exploration and exploitation is essential when navigating an uncertain world. Exploration is dysregulated in numerous neuropsychiatric disorders, many of which are sex-biased in risk, presentation, and prognosis. This raises the possibility that sex-linked mechanisms could modulate exploration differently and contribute to sex-linked individual variability in the vulnerability or resilience to these conditions. Understanding how individuals explore uncertain environments can give us in sight into how brains implement divergent exploration strategy. In this dissertation, I present three studies investigating 1. exploration strategy in a complex novel environment, 2. exploration strategy in a changing environment, 3. neuromodulatory systems underlying exploration strategy. In experiment 1 and 2, I observed a spectrum of strategies that individuals adopted to navigate the environment and sex captured a major source of variability in the strategies adopted. Both sexes did not differ in the ability to learn the task but they differed in the preferred strategy employed to explore an uncertain environment. Females preferred a more energy-conserving, systematic and exploitative approach across both tasks, where as males predominantly used more variable and exploratory approach. In experiment 3, I modulated tonic dopamine and norepinephrine level and examined the modulatory effect on exploration. The results suggested novel role of dopamine in mediating exploration and highlighted the sex-differentiated modulatory effect of norepinephrine on exploration. This dissertation took advantage of computational tools and revealed sex-correlated variability in strategies employed when interacting with an uncertain environment, rather than any difference in ability. This highlighted sex as source of individual variability and implicated potential sex-modulated circuits and systems that could contribute to vulnerability or risk for neuropsychiatric disorders.