Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

Damian Refojo; Martin Schweizer; Claudia Kuehne; Stefanie Ehrenberg; Christoph Thoeringer; Annette M. Vogl; Nina Dedic; Marion Schumacher; Gregor Von Wolff; Charilaos Avrabos; Chadi Touma; David Engblom; Günther Schütz; Klaus Armin Nave; Matthias Eder; Carsten T. Wotjak; Inge Sillaber; Florian Holsboer; Wolfgang Wurst; Jan M. Deussing

doi:10.1126/science.1202107

Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

Damian Refojo, Martin Schweizer, Claudia Kuehne, Stefanie Ehrenberg, Christoph Thoeringer, Annette M. Vogl, Nina Dedic, Marion Schumacher, Gregor Von Wolff, Charilaos Avrabos, Chadi Touma, David Engblom, Günther Schütz, Klaus Armin Nave, Matthias Eder, Carsten T. Wotjak, Inge Sillaber, Florian Holsboer, Wolfgang Wurst, Jan M. Deussing

Chair of Developmental Genetics

Research output: Contribution to journal › Article › peer-review

258 Scopus citations

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.

Original language	English
Pages (from-to)	1903-1907
Number of pages	5
Journal	Science
Volume	333
Issue number	6051
DOIs	https://doi.org/10.1126/science.1202107
State	Published - 30 Sep 2011

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Refojo, D., Schweizer, M., Kuehne, C., Ehrenberg, S., Thoeringer, C., Vogl, A. M., Dedic, N., Schumacher, M., Von Wolff, G., Avrabos, C., Touma, C., Engblom, D., Schütz, G., Nave, K. A., Eder, M., Wotjak, C. T., Sillaber, I., Holsboer, F., Wurst, W., & Deussing, J. M. (2011). Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1. Science, 333(6051), 1903-1907. https://doi.org/10.1126/science.1202107

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title = "Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1",

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.",

author = "Damian Refojo and Martin Schweizer and Claudia Kuehne and Stefanie Ehrenberg and Christoph Thoeringer and Vogl, {Annette M.} and Nina Dedic and Marion Schumacher and {Von Wolff}, Gregor and Charilaos Avrabos and Chadi Touma and David Engblom and G{\"u}nther Sch{\"u}tz and Nave, {Klaus Armin} and Matthias Eder and Wotjak, {Carsten T.} and Inge Sillaber and Florian Holsboer and Wolfgang Wurst and Deussing, {Jan M.}",

year = "2011",

month = sep,

day = "30",

doi = "10.1126/science.1202107",

language = "English",

volume = "333",

pages = "1903--1907",

journal = "Science",

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Refojo, D, Schweizer, M, Kuehne, C, Ehrenberg, S, Thoeringer, C, Vogl, AM, Dedic, N, Schumacher, M, Von Wolff, G, Avrabos, C, Touma, C, Engblom, D, Schütz, G, Nave, KA, Eder, M, Wotjak, CT, Sillaber, I, Holsboer, F, Wurst, W & Deussing, JM 2011, 'Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1', Science, vol. 333, no. 6051, pp. 1903-1907. https://doi.org/10.1126/science.1202107

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T1 - Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

AU - Refojo, Damian

AU - Schweizer, Martin

AU - Kuehne, Claudia

AU - Ehrenberg, Stefanie

AU - Thoeringer, Christoph

AU - Vogl, Annette M.

AU - Dedic, Nina

AU - Schumacher, Marion

AU - Von Wolff, Gregor

AU - Avrabos, Charilaos

AU - Touma, Chadi

AU - Engblom, David

AU - Schütz, Günther

AU - Nave, Klaus Armin

AU - Eder, Matthias

AU - Wotjak, Carsten T.

AU - Sillaber, Inge

AU - Holsboer, Florian

AU - Wurst, Wolfgang

AU - Deussing, Jan M.

PY - 2011/9/30

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N2 - 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.

AB - 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.

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JF - Science

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Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

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