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Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1

Science, 30 September 2011
Vol. 333, Issue 6051, p. 1903-1907
DOI: 10.1126/science.1202107

Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1

  1. Damian Refojo1,
  2. Martin Schweizer1,2,
  3. Claudia Kuehne1,
  4. Stefanie Ehrenberg1,
  5. Christoph Thoeringer1,
  6. Annette M. Vogl1,
  7. Nina Dedic1,
  8. Marion Schumacher1,
  9. Gregor von Wolff1,
  10. Charilaos Avrabos1,
  11. Chadi Touma1,
  12. David Engblom3,
  13. Günther Schütz3,
  14. Klaus-Armin Nave4,
  15. Matthias Eder1,
  16. Carsten T. Wotjak1,
  17. Inge Sillaber1,2,
  18. Florian Holsboer1,
  19. Wolfgang Wurst1,5,6,7,
  20. Jan M. Deussing1,*
  1. 1Max Planck Institute of Psychiatry, Munich, Germany.
  2. 2Affectis Pharmaceuticals, Munich, Germany.
  3. 3Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany.
  4. 4Department of Neurogenetics, Max Planck Institute for Experimental Medicine, Göttingen, Germany.
  5. 5Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Developmental Genetics, Neuherberg, Germany.
  6. 6Technical University Weihenstephan, Institut für Entwicklungsgenetik, Neuherberg, Germany.
  7. 7DZNE-Demenzzentrum, München, Germany.
  1. *To whom correspondence should be addressed. E-mail: deussing{at}mpipsykl.mpg.de

Abstract

The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid–containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.

  • Received for publication 23 December 2010.
  • Accepted for publication 18 August 2011.

Citation:

D. Refojo, M. Schweizer, C. Kuehne, S. Ehrenberg, C. Thoeringer, A. M. Vogl, N. Dedic, M. Schumacher, G. von Wolff, C. Avrabos, C. Touma, D. Engblom, G. Schütz, K.-A. Nave, M. Eder, C. T. Wotjak, I. Sillaber, F. Holsboer, W. Wurst, and J. M. Deussing, Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1. Science 333, 1903-1907 (2011).

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