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

Munir Gunes Kutlu, Jennifer Tat, Brooke A. Christensen, Jennifer E. Zachry, Erin S. Calipari

2023Cell Reports34 citationsDOIOpen Access PDF

Abstract

Dopamine release in the nucleus accumbens (NAc) is causally linked to adaptive aversive learning, and its dysregulation is a core phenotype in anxiety and stress disorders. Here, we record NAc core dopamine during a task where mice learn to discriminate between cues signaling two types of outcomes: (1) footshock presentation and (2) footshock omission. We show that dopamine release is evoked by footshock omission. This dopamine response is largest when the omission is unexpected and decreases over learning, and artificially increasing this signal disrupts discrimination learning. Conversely, optogenetic inhibition of dopamine responses to the footshock itself impairs learning. Finally, theory-driven computational modeling suggests that these effects can be explained by dopamine signaling the perceived saliency of predicted aversive events. Together, we elucidate the role of NAc dopamine in aversive learning and offer potential avenues for understanding the neural mechanisms involved in anxiety and stress disorders.

Topics & Concepts

DopamineNucleus accumbensOptogeneticsNeurosciencePsychologyAversive StimulusAnxietyPsychiatryNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingMemory and Neural Mechanisms