For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
107
views
4
references
 Top references
cited by
313
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      152
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Distinct roles for direct and indirect pathway striatal neurons in reinforcement

      research-article
      Author(s): 1 , 1 , 3 , 1 , 2 , 3 , □
      Publication date PMC-release:
      Journal: Nature neuroscience

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Dopamine signaling is implicated in reinforcement learning, but the neural substrates targeted by dopamine are poorly understood. Here, we bypassed dopamine signaling itself and tested how optogenetic activation of dopamine D1- or D2-receptor-expressing striatal projection neurons influenced reinforcement learning in mice. Stimulating D1-expressing neurons induced persistent reinforcement, whereas stimulating D2-expressing neurons induced transient punishment, demonstrating that activation of these circuits is sufficient to modify the probability of performing future actions.

          Related collections

          Most cited references4

          • Record: found
          • Abstract: found
          • Article: not found

          Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward.

          Mary Lobo, Herbert Covington, Dipesh Chaudhury … (2010)
          The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward.
          Article 0 comments Cited 262 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior.

            Takatoshi Hikida, Kensuke Kimura, Norio Wada … (2010)
            In the basal ganglia, convergent input and dopaminergic modulation of the direct striatonigral and the indirect striatopallidal pathways are critical in rewarding and aversive learning and drug addiction. To explore how the basal ganglia information is processed and integrated through these two pathways, we developed a reversible neurotransmission blocking technique, in which transmission of each pathway was selectively blocked by specific expression of transmission-blocking tetanus toxin in a doxycycline-dependent manner. The results indicated that the coordinated modulation of these two pathways was necessary for dopamine-mediated acute psychostimulant actions. This modulation, however, shifted to the predominant roles of the direct pathway in reward learning and cocaine sensitization and the indirect pathway in aversive behavior. These two pathways thus have distinct roles: the direct pathway critical for distinguishing associative rewarding stimuli from nonassociative ones and the indirect pathway for rapid memory formation to avoid aversive stimuli.
            Article 0 comments Cited 201 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization

              SM Ferguson, D Eskenazi, M. Ishikawa … (2010)
              The dorsal striatum plays an important role in the development of drug addiction; however, a precise understanding of the roles of striatopallidal (indirect) and striatonigral (direct) pathway neurons in regulating behaviors remains elusive. Using a novel approach that relies on the viral-mediated expression of an engineered GPCR (hM4D), we demonstrated that activation of hM4D receptors with clozapine-N-oxide (CNO) potently reduced striatal neuron excitability. When hM4D receptors were selectively expressed in either direct or indirect pathway neurons in rats, CNO did not change acute locomotor responses to amphetamine but altered behavioral plasticity associated with repeated drug treatment. Specifically, transiently disrupting striatopallidal neuronal activity facilitated behavioral sensitization whereas decreasing excitability of striatonigral neurons impaired its persistence. These findings suggest that acute drug effects can be parsed from the behavioral adaptations associated with repeated drug exposure and highlight the utility of this approach for deconstructing neuronal pathway contributions to behaviors such as sensitization.
              Article 0 comments Cited 120 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9809671
                Journal ID (pubmed-jr-id): 21092
                Journal ID (nlm-ta): Nat Neurosci
                Journal ID (iso-abbrev): Nat. Neurosci.
                Title: Nature neuroscience
                ISSN (Print): 1097-6256
                ISSN (Electronic): 1546-1726
                Publication date Nihms-submitted: 5 April 2012
                Publication date (Print): June 2012
                Publication date PMC-release: 01 December 2012
                Volume: 15
                Issue: 6
                Pages: 816-818
                Affiliations
                [1 ]Gladstone Institute of Neurological Disease
                [2 ]Departments of Physiology and Neurology, University of California, San Francisco
                [3 ]Neuroscience Graduate Program, University of California, San Francisco
                Author notes
                [□ ]To whom correspondence should be addressed: Gladstone Institute of Neurological Disease, 1650 Owens St., San Francisco, CA 94158, Tel: 415-734-2507, Fax: 415-355-0824, akreitzer@ 123456gladstone.ucsf.edu
                [*]

                These authors contributed equally to this work

                Article
                Manuscript ID: NIHMS368578
                DOI: 10.1038/nn.3100
                PMC ID: 3410042
                PubMed ID: 22544310
                SO-VID: d733002d-c9c8-4a36-84ae-72aa242ea1b7
                License:

                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
                Categories
                Subject: Article

                ScienceOpen disciplines: Neurosciences
                Data availability:
                ScienceOpen disciplines: Neurosciences

                Comments

                Comment on this article

                scite_

                Similar content152

                See all similar

                Cited by307

                See all cited by

                Most referenced authors260

                See all reference authors