Neural Mechanisms of Approach and Avoidance

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Gentry, Ronny
Roesch, Matthew R
Using environmental cues to acquire good things and avoid harmful things is critical for survival. Rewards and punishments both drive behavior through reinforcement learning mechanisms and sometimes occur together in the environment, but it remains unclear how these signals are encoded within the brain and if signals for positive and negative reinforcement are encoded similarly. The dopaminergic system and, more broadly, the corticomesolimbic circuit are known to be involved in the processing of positive and negative reinforcement. Here, I investigated neural correlates of decision-making and associated behavioral patterns within two key corticomesolimbic regions: the ventromedial prefrontal cortex (vmPFC), which is thought to generate contextually appropriate responses, and the nucleus accumbens (NAc), which is thought to use dopamine (DA) prediction error signals to motivate behavior. The goal of this work was to uncover the underlying brain mechanisms encoding positive and negative reinforcement signals and to explore individual differences in neural and behavioral patterns that arise during learning and performance. To achieve this, I recorded from single neurons within vmPFC and measured DA release within NAc core during two behavioral tasks examining distinct aspects of learning: initial Pavlovian responses, as well as more complex combined positive and negative reinforcement. I found that, within the vmPFC, cell firing was modulated more often and more robustly by cues predicting reward than by cues preceding avoidable shock; overall, we found very few cells that responded to shock cues, and responses to shock avoidance and reward cues were not colocalized within the same cells. Alternatively, I found that DA release within the NAc increased to both reward and shock avoidance cues compared to neutral cues, and these changes occurred within the same microdomain of the NAc. Additionally, we uncovered intriguing individual differences in NAc DA release and behavioral responses during both our combined approach avoidance and autoshaping tasks and, in the final chapter, shifted these responses by manipulating task parameters and inhibiting VTA-NAc DA neurons. Together, these results help further our understanding of how differences in vmPFC activity and accumbal DA release influence cue-driven learning and behavioral performance across various contexts.