Ziemann Adam E, Allen Jason E, Dahdaleh Nader S, Drebot Iuliia I, Coryell Matthew W, Wunsch Amanda M, Lynch Cynthia M, Faraci Frank M, Howard Matthew A, Welsh Michael J, Wemmie John A
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.
Cell. 2009 Nov 25;139(5):1012-21. doi: 10.1016/j.cell.2009.10.029.
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.
杏仁核处理并引导对恐惧行为至关重要的输入和输出。然而，它是否直接感知引发恐惧的刺激尚不清楚。由于杏仁核表达酸敏感离子通道-1a（ASIC1a），且正常的恐惧反应需要ASIC1a，我们推测杏仁核可能检测到pH值降低。我们发现吸入二氧化碳会降低小鼠脑内pH值并引发恐惧行为。消除或抑制ASIC1a会显著损害这种活动，而杏仁核中局部表达的ASIC1a可挽救ASIC1a基因敲除动物的二氧化碳诱导的恐惧缺陷。缓冲pH值可减弱恐惧行为，而通过杏仁核微量注射直接降低pH值可重现二氧化碳的作用。这些数据表明杏仁核是检测高碳酸血症和酸中毒并引发行为反应的重要化学传感器。它们还从分子层面解释了二氧化碳浓度升高如何引发强烈恐惧，并为剖析焦虑症和恐慌症的根源奠定了基础。
