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      Prefrontal dopamine in associative learning and memory.

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          Abstract

          Learning to associate specific objects or actions with rewards and remembering the associations are everyday tasks crucial for our flexible adaptation to the environment. These higher-order cognitive processes depend on the prefrontal cortex (PFC) and frontostriatal circuits that connect areas in the frontal lobe with the striatum in the basal ganglia. Both structures are densely innervated by dopamine (DA) afferents that originate in the midbrain. Although the activity of DA neurons is thought to be important for learning, the exact role of DA transmission in frontostriatal circuits during learning-related tasks is still unresolved. Moreover, the neural substrates of this modulation are poorly understood. Here, we review our recent work in monkeys utilizing local pharmacology of DA agents in the PFC to investigate the cellular mechanisms of DA modulation of associative learning and memory. We show that blocking both D1 and D2 receptors in the lateral PFC impairs learning of new stimulus-response associations and cognitive flexibility, but not the memory of highly familiar associations. In addition, D2 receptors may also contribute to motivation. The learning deficits correlated with reductions of neural information about the associations in PFC neurons, alterations in global excitability and spike synchronization, and exaggerated alpha and beta neural oscillations. Our findings provide new insights into how DA transmission modulates associative learning and memory processes in frontostriatal systems.

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          Author and article information

          Journal
          Neuroscience
          Neuroscience
          1873-7544
          0306-4522
          Dec 12 2014
          : 282
          Affiliations
          [1 ] The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: mvpuig@mit.edu.
          [2 ] Center for Neuroscience, Department of Neurobiology, Physiology and Behavior, University of California, Davis, CA 95618, USA.
          [3 ] The Picower Institute for Learning and Memory and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
          Article
          S0306-4522(14)00768-4 NIHMS632846
          10.1016/j.neuroscience.2014.09.026
          4364934
          25241063
          e11e6730-e32d-4d30-b9ae-cbf2461331b6
          Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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