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

Abstract

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.

Adolescent rats engage the orbitofrontal-striatal pathway differently than adults during impulsive actions

“…Premature actions may result from an inability to learn the task contingency or a failure to inhibit a response, despite knowledge that inappropriate responding will not be rewarded. Thus, while our previous work had not shown any associative learning deficits in adolescents 68 , we cannot rule out that learning deficits in adolescents may have contributed to some of the observed behavioral age differences.…”

The role of dopamine and endocannabinoid systems in prefrontal cortex development: Adolescence as a critical period

“…In vivo and ex vivo recordings have revealed that VTA dopamine neurons in rats have higher tonic firing rates during adolescence compared to adulthood, peaking during late adolescence (PND40-50). In addition, although adolescent rats have a similar proportion of phasic activity episodes, these are consistently longer compared to those of adults (McCutcheon and Marinelli, 2009 ; McCutcheon et al, 2012 ; Marinelli and McCutcheon, 2014 ; but see Kim et al, 2016 ; McCane et al, 2021 ). It is currently unknown whether these age-related changes are specific to different defined neuronal populations or pathways.…”

“…This may be related to changes in CB1 levels on prefrontal glutamatergic terminals in the VTA controlling the activity of dopamine neurons (Carr and Sesack, 2000 ; Heidbreder and Groenewegen, 2003 ; Gabbott et al, 2005 ; Beier et al, 2015 ). These complex changes may represent an important mechanism underlying developmental changes in VTA responses to rewarding and aversive environmental stimuli (Kim et al, 2016 ; McCane et al, 2021 ) and dopamine-related behaviors (Spear, 2000 ).…”

From Biological Synapses to “Intelligent” Robots

“…One of the ambitions of biologically inspired neural coding in models for robot control is to characterize and provide a plausible brain model for the behavioral neuroscience of reinforcement and extinction [12,13].…”