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Cortical 5-HT2A Receptor Signaling Modulates Anxiety-Like Behaviors in Mice
Noelia V. Weisstaub,1,3
Mingming Zhou,2
Alena Lira,2
Evelyn Lambe,6*
Javier González-Maeso,7
Jean-Pierre Hornung,8
Etienne Sibille,1
Mark Underwood,2
Shigeyoshi Itohara,9
William T. Dauer,5
Mark S. Ansorge,2,3
Emanuela Morelli,2,3
J. John Mann,2
Miklos Toth,10
George Aghajanian,6
Stuart C. Sealfon,7
René Hen,2,4
Jay A. Gingrich2,3
Abstract:
Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission inthe central nervous system modulates depression and anxiety-relatedbehaviors in humans and rodents, but the responsible downstreamreceptors remain poorly understood. We demonstrate that globaldisruption of 5-HT2A receptor (5HT2AR) signaling in mice reducesinhibition in conflict anxiety paradigms without affecting fear-conditionedand depression-related behaviors. Selective restoration of 5HT2ARsignaling to the cortex normalized conflict anxiety behaviors.These findings indicate a specific role for cortical 5HT2ARfunction in the modulation of conflict anxiety, consistent withmodels of cortical, "top-down" influences on risk assessment.
1 Department of Biology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA. 2 Department of Psychiatry, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA. 3 Sackler Institute Laboratories, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA. 4 Center for Neurobiology and Behavior, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA. 5 Department of Neurology, Columbia University and the New York State Psychiatric Institute, New York, NY 10032, USA. 6 Department of Psychiatry, Yale University, New Haven, CT 06520, USA. 7 Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA. 8 Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Lausanne, Switzerland. 9 Laboratory for Behavioral Genetics, Riken Brain Science Institute, Wako City, Japan 10 Department of Pharmacology, Cornell University Medical Center, New York, NY 10021, USA.
* Present address: Department of Physiology, University of Toronto,Toronto ON, M5S1A8, Canada.
Current address: Department of Psychiatry, University of Pittsburgh,Pittsburgh, PA 15213, USA.
To whom correspondence should be addressed. E-mail: jag46{at}columbia.edu
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Mark Underwood,2
Shigeyoshi Itohara,9
William T. Dauer,5
Mark S. Ansorge,2,3
Emanuela Morelli,2,3
J. John Mann,2
Miklos Toth,10
George Aghajanian,6
Stuart C. Sealfon,7
René Hen,2,4
Jay A. Gingrich2,3
Current address: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA. 
To whom correspondence should be addressed. E-mail: 
