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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

Butyric acid reduces breathing rate but does not evoke freezing. (A) Exposure to either TMT or butyric acid elicits a similar reduction in breathing rate in wild-type mice [t(5) = 0.2768, p = 0.7930, TMT n = 5, butyric acid n = 2]. (B) Exposure to TMT, but not butyric acid (BA) elicits robust freezing behavior and Asic1a disruption attenuated TMT-evoked freezing. A Two-Way ANOVA revealed an effect of genotype [F(1, 34) = 13.39, p = 0.0009, from left to right n = 10, 10, 9, 9, respectively], an effect of odor [F(1, 34) = 141.7, p < 0.0001] and a genotype by odor interaction [F(1, 34) = 10.78, p = 0.0024]. Planned contrast testing demonstrated that Asic1a−/− mice had a reduction in freezing to TMT (**p = 0.0016), but not butyric acid (BA) (p = 0.2673). (C)Asic1a disruption did not alter the effect of TMT on breathing rate [t(8) = 0.08014, p = 0.9381, n = 5 per group].
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Figure 2: Butyric acid reduces breathing rate but does not evoke freezing. (A) Exposure to either TMT or butyric acid elicits a similar reduction in breathing rate in wild-type mice [t(5) = 0.2768, p = 0.7930, TMT n = 5, butyric acid n = 2]. (B) Exposure to TMT, but not butyric acid (BA) elicits robust freezing behavior and Asic1a disruption attenuated TMT-evoked freezing. A Two-Way ANOVA revealed an effect of genotype [F(1, 34) = 13.39, p = 0.0009, from left to right n = 10, 10, 9, 9, respectively], an effect of odor [F(1, 34) = 141.7, p < 0.0001] and a genotype by odor interaction [F(1, 34) = 10.78, p = 0.0024]. Planned contrast testing demonstrated that Asic1a−/− mice had a reduction in freezing to TMT (**p = 0.0016), but not butyric acid (BA) (p = 0.2673). (C)Asic1a disruption did not alter the effect of TMT on breathing rate [t(8) = 0.08014, p = 0.9381, n = 5 per group].

Mentions: We next sought to determine if the reduction in breathing rate observed in response to TMT might also be caused by other foul odors. Therefore, we tested the effects of butyric acid, another pungent odor, which, like TMT, is aversive and induces avoidance behaviors in rats and mice (Endres and Fendt, 2009). Similar to TMT, butyric acid dramatically reduced breathing rate (Figure 2A), suggesting the effect on breathing rate generalizes to at least two aversive odors. However, in contrast to TMT, butyric acid failed to induce freezing (Figure 2B), which is consistent with previous assertions that butyric acid differs from TMT in this regard (Coryell et al., 2007; Endres and Fendt, 2009). Thus, although both aversive odors caused mice to slow their breathing rate by a similar degree, the reduction in breathing rate by itself is probably not sufficient to cause the freezing behavior seen with TMT.


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)

Butyric acid reduces breathing rate but does not evoke freezing. (A) Exposure to either TMT or butyric acid elicits a similar reduction in breathing rate in wild-type mice [t(5) = 0.2768, p = 0.7930, TMT n = 5, butyric acid n = 2]. (B) Exposure to TMT, but not butyric acid (BA) elicits robust freezing behavior and Asic1a disruption attenuated TMT-evoked freezing. A Two-Way ANOVA revealed an effect of genotype [F(1, 34) = 13.39, p = 0.0009, from left to right n = 10, 10, 9, 9, respectively], an effect of odor [F(1, 34) = 141.7, p < 0.0001] and a genotype by odor interaction [F(1, 34) = 10.78, p = 0.0024]. Planned contrast testing demonstrated that Asic1a−/− mice had a reduction in freezing to TMT (**p = 0.0016), but not butyric acid (BA) (p = 0.2673). (C)Asic1a disruption did not alter the effect of TMT on breathing rate [t(8) = 0.08014, p = 0.9381, n = 5 per group].
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Butyric acid reduces breathing rate but does not evoke freezing. (A) Exposure to either TMT or butyric acid elicits a similar reduction in breathing rate in wild-type mice [t(5) = 0.2768, p = 0.7930, TMT n = 5, butyric acid n = 2]. (B) Exposure to TMT, but not butyric acid (BA) elicits robust freezing behavior and Asic1a disruption attenuated TMT-evoked freezing. A Two-Way ANOVA revealed an effect of genotype [F(1, 34) = 13.39, p = 0.0009, from left to right n = 10, 10, 9, 9, respectively], an effect of odor [F(1, 34) = 141.7, p < 0.0001] and a genotype by odor interaction [F(1, 34) = 10.78, p = 0.0024]. Planned contrast testing demonstrated that Asic1a−/− mice had a reduction in freezing to TMT (**p = 0.0016), but not butyric acid (BA) (p = 0.2673). (C)Asic1a disruption did not alter the effect of TMT on breathing rate [t(8) = 0.08014, p = 0.9381, n = 5 per group].
Mentions: We next sought to determine if the reduction in breathing rate observed in response to TMT might also be caused by other foul odors. Therefore, we tested the effects of butyric acid, another pungent odor, which, like TMT, is aversive and induces avoidance behaviors in rats and mice (Endres and Fendt, 2009). Similar to TMT, butyric acid dramatically reduced breathing rate (Figure 2A), suggesting the effect on breathing rate generalizes to at least two aversive odors. However, in contrast to TMT, butyric acid failed to induce freezing (Figure 2B), which is consistent with previous assertions that butyric acid differs from TMT in this regard (Coryell et al., 2007; Endres and Fendt, 2009). Thus, although both aversive odors caused mice to slow their breathing rate by a similar degree, the reduction in breathing rate by itself is probably not sufficient to cause the freezing behavior seen with TMT.

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