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      Prolonged Dopamine Signalling in Striatum Signals Proximity and Value of Distant Rewards

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          Abstract

          Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors 15 . Many behaviours, however, are directed toward distant goals, for which transient signals might fail to provide sustained drive. Here we report a novel, extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved toward distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or--in rare instances--decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals exhibited spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.

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          Most cited references19

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          The debate over dopamine's role in reward: the case for incentive salience.

          Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: 'liking', learning, and 'wanting'. Does dopamine mostly mediate the hedonic impact of reward ('liking')? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli ('wanting')? Each hypothesis is evaluated here, and it is suggested that the incentive salience or 'wanting' hypothesis of dopamine function may be consistent with more evidence than either learning or 'liking'. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic 'liking' for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal 'wanting', and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive 'wanting' in addiction, but also provides opportunities for experiments to disentangle 'wanting', 'liking', and learning hypotheses. Results from studies that exploited those opportunities are described here. In short, dopamine's contribution appears to be chiefly to cause 'wanting' for hedonic rewards, more than 'liking' or learning for those rewards.
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            Getting formal with dopamine and reward.

            Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards. Dopamine neurons display a short-latency, phasic reward signal indicating the difference between actual and predicted rewards. The signal is useful for enhancing neuronal processing and learning behavioral reactions. It is distinctly different from dopamine's tonic enabling of numerous behavioral processes. Neurons in the striatum, frontal cortex, and amygdala also process reward information but provide more differentiated information for identifying and anticipating rewards and organizing goal-directed behavior. The different reward signals have complementary functions, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals. Addictive psychostimulant drugs may exert their action by amplifying the dopamine reward signal.
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              A selective role for dopamine in reward learning

              Individuals make choices and prioritize goals using complex processes that assign value to rewards and associated stimuli. During Pavlovian learning, previously neutral stimuli that predict rewards can acquire motivational properties, whereby they themselves become attractive and desirable incentive stimuli. But individuals differ in whether a cue acts solely as a predictor that evokes a conditional response, or also serves as an incentive stimulus, and this determines the degree to which a cue might bias choice or even promote maladaptive behavior. Here we use rats that differ in the incentive motivational properties they attribute to food cues to probe the role of the neurotransmitter dopamine in stimulus-reward learning. We show that intact dopamine transmission is not required for all forms of learning in which reward cues become effective predictors. Rather, dopamine acts selectively in a form of reward learning in which “incentive salience” is assigned to reward cues. In individuals with a propensity for this form of learning, reward cues come to powerfully motivate and control behavior. This work provides insight into the neurobiology of a form of reward learning that confers increased susceptibility to disorders of impulse control.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                21 August 2013
                04 August 2013
                29 August 2013
                28 February 2014
                : 500
                : 7464
                : 575-579
                Affiliations
                [1 ]McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
                [2 ]Department of Psychiatry & Behavioral Sciences and Department of Pharmacology, University of Washington, Seattle, WA 98195, USA
                Author notes
                Correspondence and requests for materials should be addressed to A.M.G. ( graybiel@ 123456mit.edu )
                Article
                NIHMS507218
                10.1038/nature12475
                3927840
                23913271
                b74e67bc-c2c9-4ed0-a67d-e205d13ddf27

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Institute of Mental Health : NIMH
                Award ID: R01 MH079292 || MH
                Funded by: National Institute of Mental Health : NIMH
                Award ID: R01 MH060379 || MH
                Funded by: National Institute on Drug Abuse : NIDA
                Award ID: R01 DA027858 || DA
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