The Amygdala Is a Chemosensor that Detects Carbon Dioxide and Acidosis to Elicit Fear Behavior

Adam E. Ziemann, Jason E. Allen, Nader S. Dahdaleh, Iuliia I. Drebot, Matthew W. Coryell, Amanda M. Wunsch, Cynthia M. Lynch, Frank M. Faraci, Matthew A. Howard, Michael J. Welsh*, John A. Wemmie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

271 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1012-1021
Number of pages10
JournalCell
Volume139
Issue number5
DOIs
StatePublished - Nov 25 2009

Keywords

  • MOLNEURO
  • SYSNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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