Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior

Kutlu, M. G.; Tat, J.; Zachry, J. E.; Calipari, E. S.

doi:10.1101/2022.04.15.488530

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bioRxiv · 10.1101/2022.04.15.488530

Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior

Kutlu, M. G.·Tat, J.·Zachry, J. E.·Calipari, E. S.

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Abstract

BackgroundThe inability to predict when aversive stimuli will and will not occur in is a hallmark of anxiety and stress disorders. Dopamine release in the nucleus accumbens (NAc) is sufficient and necessary for aversive learning and has been linked to both anxiety and stress disorder symptomatology. Thus, understanding how dopamine controls associative learning in response to aversive stimuli is critical to understanding the role of dopamine in behavior in health and disease. MethodsUsing an optical dopamine sensor combined with in-vivo fiber photometry in the NAc core of male and female C57BL/6J mice (N=38), we recorded dopamine responses to expected and omitted aversive outcomes during learning. We derived predictions from a theory-driven model of associative learning (Kutlu-Calipari-Schmajuk, KCS model) and tested the causality of these predictions using optogenetics. ResultsDopamine release was evoked by the predicted omission of aversive stimuli in a fashion that cannot be explained by dopamine as a reward-based prediction signal. The magnitude of the dopamine response during omissions scaled with predictions about the probability of their occurrence; however, dopamine did not track the associative value of predictive cues. Finally, we showed that the observed effects are causal to learned behavior and can only be explained by dopamine signaling the perceived saliency of predicted aversive events. ConclusionsWe elucidate the role of NAc core dopamine signaling in aversive learning in a theory-based and stimulus-specific fashion and offer potential avenues for understanding the neural mechanisms involved in anxiety and stress disorders.

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Kutlu, M. G., Tat, J., Zachry, J. E., Calipari, E. S.. 2022-04-16. Dopamine release at the time of a predicted aversive outcome causally controls the trajectory and expression of conditioned behavior. https://doi.org/10.1101/2022.04.15.488530

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