Exposure of animals to increased concentrations of CO2 induces fear responses, perhaps because it signals the possibility of suffocation. In humans, such exposure to CO2 can induce panic attacks in people with anxiety disorders. The brain region known as the amygdala processes neuronal signals associated with fear behaviors. Ziemann et al. now report that the amygdala itself may be the chemosensor that directly senses CO2 concentrations. Dissolved CO2 causes a decrease in the pH of the blood. Some of the authors had previously shown that the acid-sensing ion channel 1a (ASIC1a), a channel that is activated by extracellular acidosis, is expressed in abundance in the amygdala and other fear circuits in the brain. They therefore tested whether activation of ASIC1a channels in the amygdala might mediate fear responses to inhalation of CO2. Indeed, in four models of fear behavior in mice, knockout animals not expressing ASIC1a showed decreased fear responses to increased concentrations of CO2. Ziemann et al. found that increased concentrations of inhaled CO2 decreased the pH in the amygdala and that exposure of cultured neurons from the amygdala from wild-type mice (but not those of ASIC1a–/– mice) to increased concentrations of CO2 caused increased conductance of ASIC1a. Finally, the authors concluded that expression of ASIC1a in the amygdala is sufficient to promote CO2-induced fear behaviors because injections of adeno-associated virus encoding ASIC1a into the amygdala could restore CO2-induced fear responses in the knockout mice. The authors propose that ASIC1a channels may also have a more general role in fear signaling because fear responses to other stimuli were also blunted in the knockout animals. Furthermore, they suggest that the ASIC1a channel may provide a therapeutic target for treatment of anxiety disorders.
A. E. Ziemann, J. E. Allen, N. S. Dahdaleh, I. I. Drebot, M. W. Coryell, A. M. Wunsch, C. M. Lynch, F. M. Faraci, M. A. Howard III, M. J. Welsh, J. A. Wemmie, The amygdala is a chemosensor that detects carbon dioxide and acidosis to elicit fear behavior. Cell 139, 1012–1021 (2009). [PubMed]