Implications of Prefrontal Cortex Development for Adolescent Reward Seeking Behavior

Adolescence is a developmental period marked by increased impulsivity, heightened reward sensitivity, and reduced behavioral flexibility. These age-typical behavioral traits are thought to arise from ongoing maturation of brain circuits that support cognitive control and motivated behavior. Importantly two key brain regions, the medial prefrontal cortex (mPFC) and the lateral hypothalamus (LH), are still actively maturing during adolescence. In adults, the medial prefrontal cortex (mPFC) is a critical brain area, guiding impulse control, decision-making, and reward-seeking. Meanwhile the adult lateral hypothalamus (LH) is essential for driving feeding behaviors, responding to foodassociated cues, and for regulating internal states. Even though these brain regions are essential and clearly implicated in the unique behaviors observed in adolescence, we don’t know how they are functioning, or communicating with each other, to produce the adolescent behaviors we observe. We hypothesis that, during adolescence, the mPFC is unable to create the neuronal representations necessary to guide impulse control. At the same time we hypothesis that the adolescent LH, possibly driven by metabolic demand of body growth, is supporting an increased food drive at this age, which results in an LH that is hyperresponsive to reward-cues and may be overrepresenting reward contexts (including generalizing neutral cues as reward associated). Together, these circuit-level adolescent imbalances, too much “gas” (increased food drive via LH) and too little “brakes” (immature impulse control via mPFC), result in inflexible, impulsive behavior in adolescence. In turn leading to poor adaptability to changing task demands. To test this hypothesis, in Aim 1, we will use two-photon calcium imaging and optogenetic to determine how task-relevant neural representations in the mPFC evolve from adolescence to adulthood during a behavioral task that forces the individuals to suppress reward seeking responses at the incorrect timepoints in order to obtain larger rewards. In Aim 2, we examine the interplay between mPFC and LH activity. We test if LH hyperactivity is driving the increased reward responsiveness and decreased impulse behavior in adolescence, and test how mPFC-to-LH connectivity contributes to age-dependent differences in motivated behavior. By understanding how the medial prefrontal cortex and hypothalamic circuits interact across development, this work will provide new insight into the neural basis of adolescent-specific behavior and identify circuit-level mechanisms that may contribute to vulnerability for psychiatric disorders such anxiety disorders, impulse control disorders, and eating disorders that emerge during this sensitive window.