Citation

Ziemann AE, Allen JE, Dahdaleh NS, Drebot II, Coryell MW, Wunsch AM, Lynch CM, Faraci FM, Howard MA, Welsh MJ, Wemmie JA. Cell 2009; 139(5): 1012-1021.

Affiliation

Medical Scientist Training Program, Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA.

Comment In:

Cell 2009;139(5):867-9

Copyright

(Copyright © 2009, Cell Press)

DOI

10.1016/j.cell.2009.10.029

PMID

19945383

PMCID

PMC2808123

Abstract

The amygdala processes and directs inputs and outputs that are key to fear behavior. However, whether it directly senses fear-evoking stimuli is unknown. Because the amygdala expresses acid-sensing ion channel-1a (ASIC1a), and ASIC1a is required for normal fear responses, we hypothesized that the amygdala might detect a reduced pH. We found that inhaled CO(2) reduced brain pH and evoked fear behavior in mice. Eliminating or inhibiting ASIC1a markedly impaired this activity, and localized ASIC1a expression in the amygdala rescued the CO(2)-induced fear deficit of ASIC1a null animals. Buffering pH attenuated fear behavior, whereas directly reducing pH with amygdala microinjections reproduced the effect of CO(2). These data identify the amygdala as an important chemosensor that detects hypercarbia and acidosis and initiates behavioral responses. They also give a molecular explanation for how rising CO(2) concentrations elicit intense fear and provide a foundation for dissecting the bases of anxiety and panic disorders.

Language: en