Cue-Evoked Dopamine Promotes Conditioned Responding during Learning

• Published in: Neuron (Cambridge, Mass.) Mass.), 2020-04, Vol.106 (1), p.142-153.e7
• Main Authors: Morrens, Joachim, Aydin, Çağatay, Janse van Rensburg, Aliza, Esquivelzeta Rabell, José, Haesler, Sebastian
• Format: Article
• Language: English
• Subjects: Animals; Associative learning; Conditioned stimulus; cue associability; Dopamine; Latent inhibition; Neurons; Photometry; Psychotropic drugs; Reinforcement; Respiration; stimulus familiarity; stimulus novelty
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2020.01.012

Dopamine neurons mediate the association of conditioned stimuli (CS) with reward (unconditioned stimuli, US) by signaling the discrepancy between predicted and actual reward during the US. Some theoretical models suggest that learning is also influenced by the salience or associability of the CS. A hallmark of CS associability models is that they can explain latent inhibition, i.e., the observation that novel CS are more effectively learned than familiar CS. Novel CS are known to activate dopamine neurons, but whether those responses affect associative learning has not been investigated. Here, we used fiber photometry to characterize dopamine responses to inconsequential familiar and novel stimuli. Using bidirectional optogenetic modulation during conditioning, we then show that CS-evoked dopamine promotes conditioned responses. This suggests that Pavlovian conditioning is influenced by CS dopamine, in addition to US reward prediction errors. Accordingly, the absence of dopamine responses to familiar CS might explain their slower learning in latent inhibition. •Inconsequential novel, but not familiar, stimuli activate VTA and SNc dopamine neurons•Intrinsic stimulus value modulates dopamine responses to novel stimuli•Dopamine activation during familiar CS accelerates conditioning•Dopamine inhibition during novel CS decelerates conditioning Morrens et al. show that inconsequential novel stimuli evoke responses in dopamine neurons in the VTA and SNc. Performing bidirectional optogenetic manipulation during conditioning, they then demonstrate that novel stimulus-evoked dopamine promotes the development of behavioral responses, indicating that Pavlovian conditioning is influenced by CS dopamine, in addition to US reward prediction errors.