17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?

      research-article

      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

          Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18- l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity ( n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity ( n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity ( n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia).

          SIGNIFICANCE STATEMENT The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate–dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease.

          Related collections

          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          1 July 2015
          : 35
          : 26
          : 9615-9621
          Affiliations
          [1] 1Department of Psychiatry and Psychotherapy and
          [2] 2Neurology and
          [3] 3NeuroCure Cluster of Excellence in Medical Neuroscience, Charité–University Medicine Berlin, 10117 Berlin, Germany,
          [4] 4Institute of Psychology, Humboldt University, 12489 Berlin, Germany,
          [5] 5Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany,
          [6] 6Department of Nuclear Medicine, Charité–University Medicine Berlin, 12200 Berlin, Germany,
          [7] 7Center for Lifespan Psychology, Max Planck Institute for Human Development, 14195 Berlin, Germany, and
          [8] 8Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
          Author notes
          Correspondence should be addressed to Tobias Gleich, Department of Psychiatry and Psychotherapy, Charité–Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. tobias.gleich@ 123456charite.de

          Author contributions: T.G., R.C.L., R. Boehme, S.K., S.F., and J.G. designed research; T.G., L.D., R. Boehme, A.P., and R. Buchert performed research; R. Buchert, S.K., A.H., S.F., and J.G. contributed unpublished reagents/analytic tools; T.G., L.D., R.C.L., R. Buchert, and S.K. analyzed data; T.G., L.D., R.C.L., R. Boehme, A.P., R. Buchert, S.K., A.H., S.F., and J.G. wrote the paper.

          *T.G. and L.D. contributed equally to this work.

          F.S. and J.G. contributed equally to this work.

          Author information
          http://orcid.org/0000-0003-1106-0319
          http://orcid.org/0000-0001-7392-5280
          http://orcid.org/0000-0003-3286-6792
          Article
          PMC6605144 PMC6605144 6605144 0329-15
          10.1523/JNEUROSCI.0329-15.2015
          6605144
          26134644
          54506cab-e82b-488c-9381-68c0abf67312
          Copyright © 2015 the authors 0270-6474/15/359615-07$15.00/0
          History
          : 26 January 2015
          : 18 May 2015
          : 21 May 2015
          Categories
          Articles
          Systems/Circuits

          glutamate,FDOPA PET,prefrontal cortex,striatum,dopamine,MRS
          glutamate, FDOPA PET, prefrontal cortex, striatum, dopamine, MRS

          Comments

          Comment on this article