TY - JOUR
T1 - The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis
AU - Taugher, Rebecca J.
AU - Lu, Yuan
AU - Wang, Yimo
AU - Kreple, Collin J.
AU - Ghobbeh, Ali
AU - Fan, Rong
AU - Sowers, Levi P.
AU - Wemmie, John A.
PY - 2014
Y1 - 2014
N2 - Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a-/- and Asic1a+/+ mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior.
AB - Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a-/- and Asic1a+/+ mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior.
KW - ASIC1A
KW - Anxiety
KW - Bed nucleus of the stria terminalis
KW - Panic
KW - pH
UR - http://www.scopus.com/inward/record.url?scp=84905044440&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1680-14.2014
DO - 10.1523/JNEUROSCI.1680-14.2014
M3 - Article
C2 - 25080586
AN - SCOPUS:84905044440
SN - 0270-6474
VL - 34
SP - 10247
EP - 10255
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 31
ER -