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Dopamine signaling in the nucleus accumbens core mediates latent inhibition

2022; Nature Portfolio; Volume: 25; Issue: 8 Linguagem: Inglês

10.1038/s41593-022-01126-1

1546-1726

Munir Gunes Kutlu, Jennifer E. Zachry, Patrick R. Melugin, Jennifer Tat, Stephanie A. Cajigas, Atagun U. Isiktas, Dev D. Patel, Cody A. Siciliano, Geoffrey Schoenbaum, Melissa J. Sharpe, Erin S. Calipari,

Neurotransmitter Receptor Influence on Behavior

Studies investigating the neural mechanisms by which associations between cues and predicted outcomes control behavior often use associative learning frameworks to understand the neural control of behavior. These frameworks do not always account for the full range of effects that novelty can have on behavior and future associative learning. Here, in mice, we show that dopamine in the nucleus accumbens core is evoked by novel, neutral stimuli, and the trajectory of this response over time tracked habituation to these stimuli. Habituation to novel cues before associative learning reduced future associative learning, a phenomenon known as latent inhibition. Crucially, trial-by-trial dopamine response patterns tracked this phenomenon. Optogenetic manipulation of dopamine responses to the cue during the habituation period bidirectionally influenced future associative learning. Thus, dopamine signaling in the nucleus accumbens core has a causal role in novelty-based learning in a way that cannot be predicted based on purely associative factors. Kutlu, Zachry, Melugin et al. show that dopamine in the nucleus accumbens core is evoked by novel, neutral stimuli and tracks stimulus familiarity in the absence of valence-based predictions. These signals influence the speed of future learning for familiar stimuli.