TY - JOUR
T1 - Cue and reward evoked dopamine activity is necessary for maintaining learned pavlovian associations
AU - Van Zessen, Ruud
AU - Flores-Dourojeanni, Jacques P.
AU - Eekel, Timon
AU - van den Reijen, Siem
AU - Lodder, Bart
AU - Omrani, Azar
AU - Smidt, Marten P.
AU - Ramakers, Geert M.J.
AU - van der Plasse, Geoffrey
AU - Stuber, Garret D.
AU - Adan, Roger A.H.
N1 - Publisher Copyright:
© 2021 the authors.
PY - 2021/6/9
Y1 - 2021/6/9
N2 - Associating natural rewards with predictive environmental cues is crucial for survival. Dopamine (DA) neurons of the ventral tegmental area (VTA) are thought to play a crucial role in this process by encoding reward prediction errors (RPEs) that have been hypothesized to play a role in associative learning. However, it is unclear whether this signal is still necessary after animals have acquired a cue-reward association. In order to investigate this, we trained mice to learn a Pavlovian cue-reward association. After learning, mice show robust anticipatory and consummatory licking behavior. As expected, calcium activity of VTA DA neurons goes up for cue presentation as well as reward delivery. Optogenetic inhibition during the moment of reward delivery disrupts learned behavior, even in the continued presence of reward. This effect is more pronounced over trials and persists on the next training day. Moreover, outside of the task licking behavior and locomotion are unaffected. Similarly to inhibitions during the reward period, we find that inhibiting cue-induced dopamine (DA) signals robustly decreases learned licking behavior, indicating that cue-related DA signals are a potent driver for learned behavior. Overall, we show that inhibition of either of these DA signals directly impairs the expression of learned associative behavior. Thus, continued DA signaling in a learned state is necessary for consolidating Pavlovian associations.
AB - Associating natural rewards with predictive environmental cues is crucial for survival. Dopamine (DA) neurons of the ventral tegmental area (VTA) are thought to play a crucial role in this process by encoding reward prediction errors (RPEs) that have been hypothesized to play a role in associative learning. However, it is unclear whether this signal is still necessary after animals have acquired a cue-reward association. In order to investigate this, we trained mice to learn a Pavlovian cue-reward association. After learning, mice show robust anticipatory and consummatory licking behavior. As expected, calcium activity of VTA DA neurons goes up for cue presentation as well as reward delivery. Optogenetic inhibition during the moment of reward delivery disrupts learned behavior, even in the continued presence of reward. This effect is more pronounced over trials and persists on the next training day. Moreover, outside of the task licking behavior and locomotion are unaffected. Similarly to inhibitions during the reward period, we find that inhibiting cue-induced dopamine (DA) signals robustly decreases learned licking behavior, indicating that cue-related DA signals are a potent driver for learned behavior. Overall, we show that inhibition of either of these DA signals directly impairs the expression of learned associative behavior. Thus, continued DA signaling in a learned state is necessary for consolidating Pavlovian associations.
KW - Dopamine
KW - Optogenetics
KW - Pavlovian conditioning
KW - Reward prediction error
KW - Ventral tegmental area
UR - http://www.scopus.com/inward/record.url?scp=85108028317&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.2744-20.2021
DO - 10.1523/JNEUROSCI.2744-20.2021
M3 - Article
C2 - 33888609
AN - SCOPUS:85108028317
SN - 0270-6474
VL - 41
SP - 5004
EP - 5014
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 23
ER -