The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior.
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.
Ziemann
Adam E
AE
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.
Allen
Jason E
JE
Dahdaleh
Nader S
NS
Drebot
Iuliia I
II
Coryell
Matthew W
MW
Wunsch
Amanda M
AM
Lynch
Cynthia M
CM
Faraci
Frank M
FM
Howard
Matthew A
MA
Welsh
Michael J
MJ
Wemmie
John A
JA
D062565:Acid Sensing Ion Channels; D000138:Acidosis / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001008:Anxiety Disorders / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010991:Plethysmography; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism
C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D001639:Bicarbonates; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D002245:Carbon Dioxide