Glutamatergic and Dopaminergic Neurons Mediate Anxiogenic and Anxiolytic Effects of CRHR1

被引：235

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
Airan, Raag D.
Meltzer, Leslie A.
Roy, Madhuri
Gong, Yuqing
Chen, Han
Deisseroth, Karl
[J]. SCIENCE, 2007, 317 (5839) : 819 - 823
[2] CORTICOTROPIN RELEASING-FACTOR DECREASES POSTBURST HYPERPOLARIZATIONS AND EXCITES HIPPOCAMPAL-NEURONS
ALDENHOFF, JB
GRUOL, DL
RIVIER, J
VALE, W
SIGGINS, GR
[J]. SCIENCE, 1983, 221 (4613) : 875 - 877
[3] The role of corticotropin-releasing factor in depression and anxiety disorders
Arborelius, L
Owens, MJ
Plotsky, PM
Nemeroff, CB
[J]. JOURNAL OF ENDOCRINOLOGY, 1999, 160 (01) : 1 - 12
[4] New approaches to antidepressant drug discovery: beyond monoamines
Berton, O
Nestler, EJ
[J]. NATURE REVIEWS NEUROSCIENCE, 2006, 7 (02) : 137 - 151
[5] Convergent actions of orexin/hypocretin and CRF on dopamine neurons: Emerging players in addiction
Borgland, Stephanie L.
Ungless, Mark A.
Bonci, Antonello
[J]. BRAIN RESEARCH, 2010, 1314 : 139 - 144
[6] Stress and the brain:: From adaptation to disease
de Kloet, ER
Joëls, M
Holsboer, F
[J]. NATURE REVIEWS NEUROSCIENCE, 2005, 6 (06) : 463 - 475
[7] Countervailing Modulation of Ih by Neuropeptide Y and Corticotrophin-Releasing Factor in Basolateral Amygdala As a Possible Mechanism for Their Effects on Stress-Related Behaviors
Giesbrecht, Chantelle J.
Mackay, James P.
Silveira, Heika B.
Urban, Janice H.
Colmers, William F.
[J]. JOURNAL OF NEUROSCIENCE, 2010, 30 (50) : 16970 - 16982
[8] The pro-convulsant actions of corticotropin-releasing hormone in the hippocampus of infant rats
Hollrigel, GS
Chen, K
Baram, TZ
Soltesz, I
[J]. NEUROSCIENCE, 1998, 84 (01) : 71 - 79
[9] A role for brain stress systems in addiction
Koob, George F.
[J]. NEURON, 2008, 59 (01) : 11 - 34
[10] Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system
Lammel, Stephan
Hetzel, Andrea
Haeckel, Olga
Jones, Ian
Liss, Birgit
Roeper, Jochen
[J]. NEURON, 2008, 57 (05) : 760 - 773

← 1 2 3 →