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      Cellular and Synaptic Adaptations Mediating Opioid Dependence

      1 , 1 , 1

      Physiological Reviews

      American Physiological Society

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          CREB and memory.

          The cAMP responsive element binding protein (CREB) is a nuclear protein that modulates the transcription of genes with cAMP responsive elements in their promoters. Increases in the concentration of either calcium or cAMP can trigger the phosphorylation and activation of CREB. This transcription factor is a component of intracellular signaling events that regulate a wide range of biological functions, from spermatogenesis to circadian rhythms and memory. Here we review the key features of CREB-dependent transcription, as well as the involvement of CREB in memory formation. Evidence from Aplysia, Drosophila, mice, and rats shows that CREB-dependent transcription is required for the cellular events underlying long-term but not short-term memory. While the work in Aplysia and Drosophila only involved CREB function in very simple forms of conditioning, genetic and pharmacological studies in mice and rats demonstrate that CREB is required for a variety of complex forms of memory, including spatial and social learning, thus indicating that CREB may be a universal modulator of processes required for memory formation.
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            Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry.

             A Basbaum,  H Fields (1983)
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              Dopamine neurons report an error in the temporal prediction of reward during learning.

              Many behaviors are affected by rewards, undergoing long-term changes when rewards are different than predicted but remaining unchanged when rewards occur exactly as predicted. The discrepancy between reward occurrence and reward prediction is termed an 'error in reward prediction'. Dopamine neurons in the substantia nigra and the ventral tegmental area are believed to be involved in reward-dependent behaviors. Consistent with this role, they are activated by rewards, and because they are activated more strongly by unpredicted than by predicted rewards they may play a role in learning. The present study investigated whether monkey dopamine neurons code an error in reward prediction during the course of learning. Dopamine neuron responses reflected the changes in reward prediction during individual learning episodes; dopamine neurons were activated by rewards during early trials, when errors were frequent and rewards unpredictable, but activation was progressively reduced as performance was consolidated and rewards became more predictable. These neurons were also activated when rewards occurred at unpredicted times and were depressed when rewards were omitted at the predicted times. Thus, dopamine neurons code errors in the prediction of both the occurrence and the time of rewards. In this respect, their responses resemble the teaching signals that have been employed in particularly efficient computational learning models.
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                Author and article information

                Journal
                Physiological Reviews
                Physiological Reviews
                American Physiological Society
                0031-9333
                1522-1210
                January 2001
                January 2001
                : 81
                : 1
                : 299-343
                Affiliations
                [1 ]Vollum Institute, Oregon Health Sciences University, Portland, Oregon; Department of Pharmacology and The Medical Foundation, University of Sydney, Sydney, New South Wales, Australia; and Centre National de la Recherche Scientifique, Unité de Propre de Recherche 9023, Montpellier, France
                Article
                10.1152/physrev.2001.81.1.299
                © 2001

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