Anxiety disorders are the most common form of psychiatric illness and exact a huge toll on America's health. Current treatments are often inadequate suggesting more effective, more specific therapies are needed. Clinical studies have firmly established that CO2 inhalation triggers anxiety and panic attacks, and that patients with anxiety disorders are hyper-responsive to CO2. These findings suggest that a better understanding of the molecular mechanisms underlying CO2 sensitivity could lead to novel insight into the causes of anxiety disorders and possibly lead to better treatments. Because CO2 sensitivity has been explored primarily in clinical studies, which are restricted in their ability to identify molecular mechanisms, there is a significant need for animal models to probe the mechanisms underlying CO2 sensitivity. In this proposal we address this need for animal models of CO2-evoked fear, by modeling CO2 behavioral and physiological responses in mice. We investigate the hypothesis that CO2 inhalation lowers brain pH, which activates pH-sensitive receptors in the fear circuit, which in turn increase the behavioral and physiological manifestations of fear, anxiety, and panic. This project may be critical for helping to explain the long recognized, but poorly understood clinical phenomenon of CO2 sensitivity. In addition, these studies are likely to have broader implications. Our preliminary data suggest that CO2 activates novel signaling pathways underlying anxiety disorders, and that these pathways might be therapeutically targeted to prevent anxiety disorders and reduce their symptoms.

Public Health Relevance

Although it is well established that carbon dioxide (CO2) inhalation triggers anxiety and panic in anxiety disorder patients, the underlying mechanisms are not known. This proposal models CO2- evoked anxiety and panic in mice and suggests that understanding CO2-sensitivity has broad implications, including novel molecular pathways underlying anxiety disorders and new treatment targets.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-PMDA-A (01))
Program Officer
Winsky, Lois M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Schools of Medicine
Iowa City
United States
Zip Code
Heo, Hye-Young; Wemmie, John A; Johnson, Casey P et al. (2015) Eccentricity mapping of the human visual cortex to evaluate temporal dynamics of functional T1ρ mapping. J Cereb Blood Flow Metab 35:1213-9
Fiedorowicz, Jess G; Prossin, Alan R; Johnson, Casey P et al. (2015) Peripheral inflammation during abnormal mood states in bipolar I disorder. J Affect Disord 187:172-8
Johnson, C P; Follmer, R L; Oguz, I et al. (2015) Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping. Mol Psychiatry 20:201-6
Johnson, Casey P; Heo, Hye-Young; Thedens, Daniel R et al. (2014) Rapid acquisition strategy for functional T1ρ mapping of the brain. Magn Reson Imaging 32:1067-77
Kreple, Collin J; Lu, Yuan; Taugher, Rebecca J et al. (2014) Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity. Nat Neurosci 17:1083-91
Du, Jianyang; Reznikov, Leah R; Price, Margaret P et al. (2014) Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala. Proc Natl Acad Sci U S A 111:8961-6
Magnotta, Vincent A; Johnson, Casey P; Follmer, Robin et al. (2014) Functional t1ρ imaging in panic disorder. Biol Psychiatry 75:884-91
Price, M P; Gong, H; Parsons, M G et al. (2014) Localization and behaviors in null mice suggest that ASIC1 and ASIC2 modulate responses to aversive stimuli. Genes Brain Behav 13:179-94
Heo, Hye-Young; Wemmie, John; Thedens, Daniel et al. (2014) Evaluation of activity-dependent functional pH and T1ρ response in the visual cortex. Neuroimage 95:336-43
Taugher, Rebecca J; Lu, Yuan; Wang, Yimo et al. (2014) The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis. J Neurosci 34:10247-55

Showing the most recent 10 out of 17 publications