Cue and Reward Evoked Dopamine Activity Is Necessary for Maintaining Learned Pavlovian Associations

Zessen, Ruud van; Flores-Dourojeanni, Jacques P.; Eekel, Timon; Reijen, Siem van den; Lodder, Bart; Omrani, Azar; Smidt, Marten P.; Ramakers, G.J.A.; Plasse, G; Stuber, Garret D.; Adan, Roger A.H.

doi:10.1523/jneurosci.2744-20.2021

Cited by 17 publications

(13 citation statements)

References 47 publications

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“…Adolescent VTA and SN neurons are engaged differently to reach the same behavioral endpoints as adults Dopamine neurons in the VTA and SN have been implicated in operant and Pavlovian conditioning (Schultz, 1998;Dalley et al, 2002;Parkinson et al, 2002;Haruno and Kawato, 2006;Lex and Hauber, 2010;Coddington and Dudman, 2018;Keiflin et al, 2019;van Zessen et al, 2021). While much of the learning literature has focused on dopamine neurons in the VTA, multiple studies indicated that SN neurons also generate reward-related signals (Coddington and Dudman, 2018;Saunders et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In the adult brain, dopamine neurons in the VTA, which project primarily to ventral (limbic) striatal regions and represent state and action values as well as reward prediction errors, are important for reward signaling during both types of conditioning (Schultz, 1998;Pessiglione et al, 2006;Keiflin et al, 2019). Emerging data suggest that adult dopamine neurons in another midbrain region, the substantia nigra (SN), are also involved in processing reward-related learning (Coddington and Dudman, 2018;Keiflin et al, 2019;van Zessen et al, 2021). Dopamine neurons in SN primarily project to the dorsal striatum (DS).…”

Section: Introductionmentioning

confidence: 99%

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Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

et al. 2021

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Neuronal underpinning of learning cause-and-effect associations in the adolescent brain remains poorly understood. Two fundamental forms of associative learning are Pavlovian (classical) conditioning, where a stimulus is followed by an outcome, and operant (instrumental) conditioning, where outcome is contingent on action execution. Both forms of learning, when associated with a rewarding outcome, rely on midbrain dopamine neurons in the ventral tegmental area (VTA) and substantia nigra (SN). We find that, in adolescent male rats, reward-guided associative learning is encoded differently by midbrain dopamine neurons in each conditioning paradigm. Whereas simultaneously recorded VTA and SN adult neurons have a similar phasic response to reward delivery during both forms of conditioning, adolescent neurons display a muted reward response during operant but a profoundly larger reward response during Pavlovian conditioning. These results suggest that adolescent neurons assign a different value to reward when it is not gated by action. The learning rate of adolescents and adults during both forms of conditioning was similar, supporting the notion that differences in reward response in each paradigm may be because of differences in motivation and independent of state versus action value learning. Static characteristics of dopamine neurons, such as dopamine cell number and size, were similar in the VTA and SN of both ages, but there were age-related differences in stimulated dopamine release and correlated spike activity, suggesting that differences in reward responsiveness by adolescent dopamine neurons are not because of differences in intrinsic properties of these neurons but engagement of different dopaminergic networks.SIGNIFICANCE STATEMENTReckless behavior and impulsive decision-making by adolescents suggest that motivated behavioral states are encoded differently by the adolescent brain. Motivated behavior, which is dependent on the function of the dopamine system, follows learning of cause-and-effect associations in the environment. We find that dopamine neurons in adolescents encode reward differently depending on the cause-and-effect relationship of the means to receive that reward. Compared with adults, reward contingent on action led to a muted response, whereas reward that followed a cue but was not gated by action produced an augmented phasic response. These data demonstrate an age-related difference in dopamine neuron response to reward that is not uniform and is guided by processes that differentiate between state and action values.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

et al. 2021

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“…3 show that cholinergic input facilitates glutamatergic inputs induced resonator BS, indicating that glutamatergic (cholinergic) inputs can regulate the scale of glutamatergic-(cholinergic-) induced resonator BS originating from other brain regions and cholinergic inputs can regulate the scale of glutamatergic-induced resonator BS, thereby producing different amplitude of phasic DA release. In experiments, it is observed that the amplitude of DA release varies due to different reward stimuli [61] [62]. The other speculation is that, BA state would induce DA ramping signals.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of burst synchronization induced by excitatory inputs on midbrain dopamine neurons

Chen

2023

Preprint

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Dopamine (DA) signals play critical roles in reward-related behavior, decision making, and learning. Yet the mainstream notion that DA signals are encoded by the temporal dynamics of individual DA cell activity is increasingly contested with data supporting that DA signals prefer to be encoded by the spatial organization of DA neuron populations. However, how distributed and parallel excitatory afferent inputs simultaneously induce burst synchronization (BS) is unclear. Our previous work implies that the burst could presumably transition from an integrator to a resonator if the excitatory inputs increase further. Here the responses of networked DA neurons to different intensity of excitatory inputs are investigated. It is found that as NMDA conductance increases, the network will transition from resting state to burst asynchronization (BA) state and then to BS state, showing a bounded BA and BS region in the NMDA conductance space. Furthermore, it is found that as muscarinic receptors modulatedCa2+dependent cationic (CAN) conductance increases, both boundaries between resting and BA, and between BA and BS gradually decrease. Phase plane analysis on DA reduced model unveils that the burst transition to a resonator underpins the changes in the network dynamics. Slow-fast dissection analysis on DA full model uncovers that the underlying mechanism of the roles and synergy of NMDA and muscarinic receptors in inducing the burst transition emerge from the enlargement of nonlinear positive feedback relationship between moreCa2+influx provided by additional NMDA current and moreICANmodulated by added muscarinic receptors. Moreover, the lag in DA volume transmission has no effect on excitatory inputs-elicited resonator BS except for requiring more excitatory inputs. These findings shed new lights on understanding the collective behavior of DA cells population regulated by the distributed excitatory inputs, and might provide a new perspective for understanding the abnormal DA release in pathological states.Author summaryThe importance of DA signals is beyond doubt, so their encoding mechanism has very important biological significance and draws widespread attention. Yet the mainstream notion that DA cells individual provide a uniform, broadly distributed signal is increasingly contested with data supporting both homogeneity across dopamine cell activity and diversity in DA signals in target regions. Our article proposes that diverse distributed and parallel excitatory inputs can not only regulate the temporal dynamics of individual DA cell activity, but also simultaneously and synergistically regulate the network dynamics of DA cell populations by changing the local dynamics of DA cells, namely the burst transition from integrators to resonators. According to our perspective, many data that are difficult to interpret by the notion of the DA neuron individual coding can be well explained, such as burst asynchronization coding DA ramping signals, the scale of burst synchronization coding the amplitude of phase DA release, inhibitory DA autoreceptors facilitating resonator burst synchronization by postinhibitory rebound, etc. This study aims to elucidate the working mechanism of the DA system in physiological states such as positive reinforcement, and then to provide a new research perspective and foundation for understanding the abnormal DA release in pathological states.

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“…Importantly, several causal manipulations also highlight the direct involvement of DA system in reward learning and motivational processes. For example optogenetics activation or inhibition of DA midbrain neurons during a task where subjects need to learn the value of different stimuli will, respectively increase or decrease the value of the stimuli and ultimately modulate the subjects' motivation to acquire these stimuli and their associated reward (Stauffer et al, 2016;Van Zessen et al, 2021). Finally, the opposite neuro-behavioral mechanism can be observed during the presentation of a conditioned stimulus predicting an aversive event.…”

Section: Promoting Appetitive Reward Seeking and Aversive Event Avoid...mentioning

confidence: 99%

Can we tackle climate change by behavioral hacking of the dopaminergic system?

Burguière

2022

Front. Behav. Neurosci.

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Climate change is an undeniable fact that will certainly affect millions of people in the following decades. Despite this danger threatening our economies, wellbeing and our lives in general, there is a lack of immediate response at both the institutional and individual level. How can it be that the human brain cannot interpret this threat and act against it to avoid the immense negative consequences that may ensue? Here we argue that this paradox could be explained by the fact that some key brain mechanisms are potentially poorly tuned to take action against a threat that would take full effect only in the long-term. We present neuro-behavioral evidence in favor of this proposal and discuss the role of the dopaminergic (DA) system in learning accurate prediction of the value of an outcome, and its consequences regarding the climate issue. We discuss how this system discounts the value of delayed outcomes and, consequently, does not favor action against the climate crisis. Finally, according to this framework, we suggest that this view may be reconsidered and, on the contrary, that the DA reinforcement learning system could be a powerful ally if adapted to short-term incentives which promote climate-friendly behaviors. Additionally, the DA system interacts with multiple brain systems, in particular those related to higher cognitive functions, which can adjust its functions depending on psychological, social, or other complex contextual information. Thus, we propose several generic action plans that could help to hack these neuro-behavioral processes to promote climate-friendly actions.

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Cue and Reward Evoked Dopamine Activity Is Necessary for Maintaining Learned Pavlovian Associations

Cited by 17 publications

References 47 publications

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

Adolescent Dopamine Neurons Represent Reward Differently during Action and State Guided Learning

Dynamics of burst synchronization induced by excitatory inputs on midbrain dopamine neurons

Can we tackle climate change by behavioral hacking of the dopaminergic system?

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