Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1

被引：240

作者：

Refojo, Damian ^{[1
]}

Schweizer, Martin ^{[1
,2
]}

Kuehne, Claudia ^{[1
]}

Ehrenberg, Stefanie ^{[1
]}

Thoeringer, Christoph ^{[1
]}

Vogl, Annette M. ^{[1
]}

Dedic, Nina ^{[1
]}

Schumacher, Marion ^{[1
]}

von Wolff, Gregor ^{[1
]}

Avrabos, Charilaos ^{[1
]}

Touma, Chadi ^{[1
]}

Engblom, David ^{[3
]}

Schuetz, Guenther ^{[3
]}

Nave, Klaus-Armin ^{[4
]}

Eder, Matthias ^{[1
]}

Wotjak, Carsten T. ^{[1
]}

Sillaber, Inge ^{[1
,2
]}

Holsboer, Florian ^{[1
]}

Wurst, Wolfgang ^{[1
,5
,6
,7
]}

Deussing, Jan M. ^{[1
]}

机构：

[1] Max Planck Inst Psychiat, Munich, Germany

[2] Affectis Pharmaceut, Munich, Germany

[3] German Canc Res Ctr, Div Mol Biol Cell 1, D-6900 Heidelberg, Germany

[4] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany

[5] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Dev Genet, Neuherberg, Germany

[6] Tech Univ Weihenstephan, Inst Entwicklungsgenet, Neuherberg, Germany

[7] DZNE Demenzzentrum, Munich, Germany

来源：

SCIENCE | 2011年 / 333卷 / 6051期

关键词：

CORTICOTROPIN-RELEASING-FACTOR; FACTOR RECEPTOR 1-DEFICIENT; IMPAIRED STRESS-RESPONSE; MICE LACKING; I-H; HORMONE; ANXIETY; BRAIN; BEHAVIOR; CRF;

D O I：

10.1126/science.1202107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 gamma-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.

引用

页码：1903 / 1907

页数：5

共 30 条

[1] High-speed Imaging reveals neurophysiological links to behavior in an animal model of depression [J].