Wednesday, January 15, 2025
1/15/2025
PROJECT SUMMARY (See instructions): The neuronal circuitry underlying motivational processes in adolescent models is understudied but clinically relevant because disorders such as depression, schizophrenia, and substance use disorder, which are marked by alterations in motivation, emerge during adolescence. The frontal cortex and striatum are critical targets because they are amongst the last regions to mature. My previous work investigated how orbitofrontal cortex (OFC)-dorsomedial (DMS) circuits guide goal-directed processes and control response inhibition in adolescent and adult rats. Additionally, I investigated the impact of adolescent alcohol exposure on these networks. I found that adolescent alcohol exposure is associated with age-specific changes in OFC and DMS response to conditioned stimuli and reward. In a separate study, I recorded from dopamine neurons and observed that adolescents exhibited a larger phasic response to reward in a stimulus-driven task, while adults exhibit a larger response when reward is acquired during a goal-driven task. Collectively, these data suggest adolescent alcohol exposure promotes lasting changes in OFC-DMS circuits, and that adolescents and adults employ different computational strategies during reward-seeking, likely due to age-specific activity in cortical-striatal circuits. The proposed projects use a combination of computational modeling, chemogenetics and in vivo electrophysiology recordings to test the hypotheses that (1) developmental maturation is characterized by an enhanced ability to employ goal-directed control of behavior and (2) adolescent alcohol exposure causes pathology in neural circuits required for goaldirected control. These experiments will further elucidate the relationship between goal-directed processes, adolescent alcohol exposure and risk of addiction-related behaviors. Using previously acquired recordings of the OFC and DMS in adult and adolescent rats (K99), I will integrate experimental and computational approaches to model neural strategies underlying motivated behavior in adolescents and adults (Aim 1). Next, I will use chemogenetics to test the model predictions and determine causality between behavior and physiology (Aim 2). Lastly, I will determine how engagement of different computational strategies is impacted by adolescent alcohol exposure (Aim 3). These translational results will enhance our mechanistic and computational understanding of adolescent brain function which is fundamental for understanding the etiology and pathophysiology of disorders with an adolescent onset, such as addiction.
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