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ASIC1A in the bed nucleus of the stria terminalis mediates TMT-evoked freezing.

Taugher RJ, Ghobbeh A, Sowers LP, Fan R, Wemmie JA - Front Neurosci (2015)

Bottom Line: Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing.However, unlike TMT, butyric acid did not induce freezing.We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Iowa Iowa City, IA, USA ; Department of Veterans Affairs Medical Center Iowa City, IA, USA.

ABSTRACT
Mice display an unconditioned freezing response to TMT, a predator odor isolated from fox feces. Here we found that in addition to freezing, TMT caused mice to decrease breathing rate, perhaps because of the aversive smell. Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing. Interestingly, butyric acid, another foul odor, also caused mice to reduce breathing rate. However, unlike TMT, butyric acid did not induce freezing. Thus, although these aversive odors may affect breathing, the unpleasant smell and suppression of breathing by themselves are insufficient to cause freezing. Because the acid-sensing ion channel-1A (ASIC1A) has been previously implicated in TMT-evoked freezing, we tested whether Asic1a disruption also altered breathing. We found that TMT reduced breathing rate in both Asic1a(+/+) and Asic1a(-/-) mice, suggesting that ASIC1A is not required for TMT to inhibit breathing and that the absence of TMT-evoked freezing in the Asic1a(-/-) mice is not due to an inability to detect TMT. These observations further indicate that ASIC1A must affect TMT freezing in another way. Because the bed nucleus of the stria terminalis (BNST) has been critically implicated in TMT-evoked freezing and robustly expresses ASIC1A, we tested whether ASIC1A in the BNST plays a role in TMT-evoked freezing. We disrupted ASIC1A in the BNST of Asic1a(loxP/loxP) mice by delivering Cre recombinase to the BNST with an adeno-associated virus (AAV) vector. We found that disrupting ASIC1A in the BNST reduced TMT-evoked freezing relative to control mice in which a virus expressing eGFP was injected. To test whether ASIC1A in the BNST was sufficient to increase TMT-evoked freezing, we used another AAV vector to express ASIC1A in the BNST of Asic1a(-/-) mice. We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing. Together, these data suggest that the BNST is a key site of ASIC1A action in TMT-evoked freezing.

No MeSH data available.


Related in: MedlinePlus

TMT reduces breathing and evokes freezing. (A) Representative plethysmography traces from a sham mouse in air and TMT. (B) TMT exposure dramatically reduces respiratory rate. This reduction in breathing rate is attenuated by olfactory bulb lesions [One-tailed t-test, t(4) = 2.239, *p = 0.0443, n = 5 per group]. (C) TMT also evoked freezing which was largely abolished by olfactory bulb lesions [t(9) = 7.069, ***p < 0.0001, sham n = 6, lesion n = 5].
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Figure 1: TMT reduces breathing and evokes freezing. (A) Representative plethysmography traces from a sham mouse in air and TMT. (B) TMT exposure dramatically reduces respiratory rate. This reduction in breathing rate is attenuated by olfactory bulb lesions [One-tailed t-test, t(4) = 2.239, *p = 0.0443, n = 5 per group]. (C) TMT also evoked freezing which was largely abolished by olfactory bulb lesions [t(9) = 7.069, ***p < 0.0001, sham n = 6, lesion n = 5].

Mentions: While observing mice during TMT exposure, we noticed that they appeared to breathe less frequently than during exposure to compressed air alone. Thus, we used whole-body plethysmography to quantify the effects of TMT on breathing rate, and indeed TMT exposure dramatically reduced rate of breathing (Figures 1A,B). In air, mice continuously took quick, rhythmic breaths, whereas in TMT, mice exhaled more slowly and there were distinct pauses between breaths (Figure 1A). Volume measurements were not possible with our plethysmographic set-up. Thus, it is not clear whether the reduction in breathing rate was accompanied by volume changes, although for each mouse it appeared that the amplitude of individual breaths did not change very much. This suggests an overall decrease in minute ventilation (rate × volume). Because a recent study in rats found that olfactory bulb lesions eliminated TMT-evoked freezing (Ayers et al., 2013), we wondered whether TMT effects on breathing rate might also depend on the olfactory bulb. Therefore, we lesioned the olfactory bulb bilaterally and tested breathing rate. We found that olfactory bulb lesions significantly attenuated effects of TMT on breathing rate (Figure 1B), as well as freezing (Figure 1C). Together, these observations are consistent with previous studies suggesting that effects of TMT depend on olfaction and extend those observations to another effect of TMT, reduction in breathing rate.


ASIC1A in the bed nucleus of the stria terminalis mediates TMT-evoked freezing.

Taugher RJ, Ghobbeh A, Sowers LP, Fan R, Wemmie JA - Front Neurosci (2015)

TMT reduces breathing and evokes freezing. (A) Representative plethysmography traces from a sham mouse in air and TMT. (B) TMT exposure dramatically reduces respiratory rate. This reduction in breathing rate is attenuated by olfactory bulb lesions [One-tailed t-test, t(4) = 2.239, *p = 0.0443, n = 5 per group]. (C) TMT also evoked freezing which was largely abolished by olfactory bulb lesions [t(9) = 7.069, ***p < 0.0001, sham n = 6, lesion n = 5].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508508&req=5

Figure 1: TMT reduces breathing and evokes freezing. (A) Representative plethysmography traces from a sham mouse in air and TMT. (B) TMT exposure dramatically reduces respiratory rate. This reduction in breathing rate is attenuated by olfactory bulb lesions [One-tailed t-test, t(4) = 2.239, *p = 0.0443, n = 5 per group]. (C) TMT also evoked freezing which was largely abolished by olfactory bulb lesions [t(9) = 7.069, ***p < 0.0001, sham n = 6, lesion n = 5].
Mentions: While observing mice during TMT exposure, we noticed that they appeared to breathe less frequently than during exposure to compressed air alone. Thus, we used whole-body plethysmography to quantify the effects of TMT on breathing rate, and indeed TMT exposure dramatically reduced rate of breathing (Figures 1A,B). In air, mice continuously took quick, rhythmic breaths, whereas in TMT, mice exhaled more slowly and there were distinct pauses between breaths (Figure 1A). Volume measurements were not possible with our plethysmographic set-up. Thus, it is not clear whether the reduction in breathing rate was accompanied by volume changes, although for each mouse it appeared that the amplitude of individual breaths did not change very much. This suggests an overall decrease in minute ventilation (rate × volume). Because a recent study in rats found that olfactory bulb lesions eliminated TMT-evoked freezing (Ayers et al., 2013), we wondered whether TMT effects on breathing rate might also depend on the olfactory bulb. Therefore, we lesioned the olfactory bulb bilaterally and tested breathing rate. We found that olfactory bulb lesions significantly attenuated effects of TMT on breathing rate (Figure 1B), as well as freezing (Figure 1C). Together, these observations are consistent with previous studies suggesting that effects of TMT depend on olfaction and extend those observations to another effect of TMT, reduction in breathing rate.

Bottom Line: Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing.However, unlike TMT, butyric acid did not induce freezing.We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, University of Iowa Iowa City, IA, USA ; Department of Veterans Affairs Medical Center Iowa City, IA, USA.

ABSTRACT
Mice display an unconditioned freezing response to TMT, a predator odor isolated from fox feces. Here we found that in addition to freezing, TMT caused mice to decrease breathing rate, perhaps because of the aversive smell. Consistent with this possibility, olfactory bulb lesions attenuated this effect of TMT, as well as freezing. Interestingly, butyric acid, another foul odor, also caused mice to reduce breathing rate. However, unlike TMT, butyric acid did not induce freezing. Thus, although these aversive odors may affect breathing, the unpleasant smell and suppression of breathing by themselves are insufficient to cause freezing. Because the acid-sensing ion channel-1A (ASIC1A) has been previously implicated in TMT-evoked freezing, we tested whether Asic1a disruption also altered breathing. We found that TMT reduced breathing rate in both Asic1a(+/+) and Asic1a(-/-) mice, suggesting that ASIC1A is not required for TMT to inhibit breathing and that the absence of TMT-evoked freezing in the Asic1a(-/-) mice is not due to an inability to detect TMT. These observations further indicate that ASIC1A must affect TMT freezing in another way. Because the bed nucleus of the stria terminalis (BNST) has been critically implicated in TMT-evoked freezing and robustly expresses ASIC1A, we tested whether ASIC1A in the BNST plays a role in TMT-evoked freezing. We disrupted ASIC1A in the BNST of Asic1a(loxP/loxP) mice by delivering Cre recombinase to the BNST with an adeno-associated virus (AAV) vector. We found that disrupting ASIC1A in the BNST reduced TMT-evoked freezing relative to control mice in which a virus expressing eGFP was injected. To test whether ASIC1A in the BNST was sufficient to increase TMT-evoked freezing, we used another AAV vector to express ASIC1A in the BNST of Asic1a(-/-) mice. We found region-restricted expression of ASIC1A in the BNST increased TMT-elicited freezing. Together, these data suggest that the BNST is a key site of ASIC1A action in TMT-evoked freezing.

No MeSH data available.


Related in: MedlinePlus