Orbitofrontal and Prelimbic Cortices Serve Complementary Roles in Adapting Reward Seeking to Learned Anxiety

In dynamic environments where stimuli predicting rewarding or aversive outcomes unexpectedly change, it is critical to flexibly update behavior while preserving recollection of previous associations. Dopamine and GABA neurons in the ventral tegmental area (VTA) are implicated in reward and punishment learning, yet little is known about how each population adapts when the predicted outcome valence changes. We measured VTA dopamine and GABA population activity while male and female rats learned to associate three discrete auditory cues to three distinct outcomes: reward, punishment, or no outcome within the same session. After learning, the reward and punishment cue-outcome contingencies were reversed, and subsequently re-reversed. As expected, the dopamine population rapidly adapted to learning and contingency reversals by increasing the response to appetitive stimuli and decreasing the response to aversive stimuli. In contrast, the GABA population increased activity to all sensory events regardless of valence, including the neutral cue. Reversing learned contingencies selectively influenced GABA responses to the reward-predictive cue, prolonging increased activity within and across sessions. The observed valence-specific dissociations in the directionality and temporal progression of VTA dopamine and GABA calcium activity indicates that these populations are independently recruited and serve distinct roles during appetitive and aversive associative learning and contingency reversal.

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The Role of the Orbitofrontal Cortex in the Regulation of Fear Coping Strategies

Kuan,

Chang

2024

Journal of Physiological Investigation

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Under threats, individuals exhibit freezing behavior and prepare for active coping. The ability to flexibly shift between freezing and active coping increases survival chances in animals and decreases susceptibility to mental disorders among human beings. For example, patients with psychiatric disorders, such as obsessive-compulsive disorder and posttraumatic stress disorder, often show maladaptive coping behaviors. The orbitofrontal cortex (OFC) is a critical hub to process higher cognitive functions, sensory inputs, reward learning, and decision-making. It also regulates negative emotions and its aberrant activation level often correlates with numerous mental disorders. The rodent OFC comprises different subdivisions with varying connections to cortical and subcortical regions. Among these subdivisions, the medial orbital area (MO) and the lateral orbital area (LO) have distinct functions in the regulation of fear. Here, we updated the existing rodent literature studying the function of the OFC, with a particular focus on the MO and the LO in different coping strategies of animals. By examining the role of the OFC in the mediation of defensive coping strategies, we aim to deepen the understanding of its functional importance on mental health.

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Orbitofrontal and Prelimbic Cortices Serve Complementary Roles in Adapting Reward Seeking to Learned Anxiety

Cited by 3 publications

References 81 publications

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Effects of psilocybin on uncertain punishment learning

Reward and punishment contingency shifting reveals distinct roles for VTA dopamine and GABA neurons in behavioral flexibility

The Role of the Orbitofrontal Cortex in the Regulation of Fear Coping Strategies

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