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A fear-inducing odor alters PER2 and c-Fos expression in brain regions involved in fear memory.

Pantazopoulos H, Dolatshad H, Davis FC - PLoS ONE (2011)

Bottom Line: These changes were accompanied by increased c-Fos expression at ZT0.In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group.The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America. hantazo@mclean.harvard.edu

ABSTRACT
Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT) at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus.

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TMT exposure alters expression of PER2 and c-Fos in the BLA.TMT altered the rhythm and amount of expression of PER2 in the BLA resulting in significantly lower expression at ZT 0 for the TMT0 group and significantly higher expression at ZT 6 and ZT 12 for both experimental groups (A). TMT exposure also resulted in an increase of c-Fos expression at ZT 0 for both groups, with the increase for the TMT0 group significantly higher than the TMT12 group (B). Photomicrographs showing low amount of PER2 immunoreactivity in the BLA of a TMT 0 animal at ZT 0 (C) and normal amount of immunoreactivity the same timepoint for a TMT12 animal (D). Photomicrographs showing increased c-Fos expression at ZT 0 in the BLA of a TMT0 animal (E) and lower level of expression at ZT 0 in a TMT12 animal (F). *significantly different from control group at that time point (p<0.05) **significantly different from control and experimental group at that timepoint (p<0.05). The values for ZT 0 are repeated as ZT 24. Error bars represent standard errors.
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pone-0020658-g003: TMT exposure alters expression of PER2 and c-Fos in the BLA.TMT altered the rhythm and amount of expression of PER2 in the BLA resulting in significantly lower expression at ZT 0 for the TMT0 group and significantly higher expression at ZT 6 and ZT 12 for both experimental groups (A). TMT exposure also resulted in an increase of c-Fos expression at ZT 0 for both groups, with the increase for the TMT0 group significantly higher than the TMT12 group (B). Photomicrographs showing low amount of PER2 immunoreactivity in the BLA of a TMT 0 animal at ZT 0 (C) and normal amount of immunoreactivity the same timepoint for a TMT12 animal (D). Photomicrographs showing increased c-Fos expression at ZT 0 in the BLA of a TMT0 animal (E) and lower level of expression at ZT 0 in a TMT12 animal (F). *significantly different from control group at that time point (p<0.05) **significantly different from control and experimental group at that timepoint (p<0.05). The values for ZT 0 are repeated as ZT 24. Error bars represent standard errors.

Mentions: Repeated exposure to TMT at ZT 0 essentially reversed the normal rhythm of PER2 expression in the BLA (Figure 3 A, C & D, Table 1) with a peak of expression occurring at ZT 6 and the lowest point of expression at ZT 0. The amount of PER2-IR was significantly lower than control mice at ZT 0, and significantly higher than control mice at ZT 6 and ZT 12 (Figure 3 A). In comparison, results for the TMT12 group were different. PER2 in the TMT12 group remained at control levels in the BLA at ZT 0 and ZT 18 but did not have the normal decrease in PER2 expression at ZT 6 and ZT12, which resulted in essence, a lack of rhythmic PER2 expression, with expression remaining relatively high at all timepoints. (Figure 3, Table 1). The amount of PER2-IR was significantly higher at ZT 0 compared to the TMT0 group, and significantly higher at ZT 6 and ZT 12 compared to the control group (Figure 3 A). Changes in PER2 expression in response to TMT exposure were accompanied by increased c-Fos expression only at ZT 0 for both experimental groups, with the increase in the TMT0 group significantly greater than both the control and TMT12 groups (Figure 3 B). The rhythm of c-Fos expression in the BLA however was not affected by TMT exposure (Table 2).


A fear-inducing odor alters PER2 and c-Fos expression in brain regions involved in fear memory.

Pantazopoulos H, Dolatshad H, Davis FC - PLoS ONE (2011)

TMT exposure alters expression of PER2 and c-Fos in the BLA.TMT altered the rhythm and amount of expression of PER2 in the BLA resulting in significantly lower expression at ZT 0 for the TMT0 group and significantly higher expression at ZT 6 and ZT 12 for both experimental groups (A). TMT exposure also resulted in an increase of c-Fos expression at ZT 0 for both groups, with the increase for the TMT0 group significantly higher than the TMT12 group (B). Photomicrographs showing low amount of PER2 immunoreactivity in the BLA of a TMT 0 animal at ZT 0 (C) and normal amount of immunoreactivity the same timepoint for a TMT12 animal (D). Photomicrographs showing increased c-Fos expression at ZT 0 in the BLA of a TMT0 animal (E) and lower level of expression at ZT 0 in a TMT12 animal (F). *significantly different from control group at that time point (p<0.05) **significantly different from control and experimental group at that timepoint (p<0.05). The values for ZT 0 are repeated as ZT 24. Error bars represent standard errors.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105109&req=5

pone-0020658-g003: TMT exposure alters expression of PER2 and c-Fos in the BLA.TMT altered the rhythm and amount of expression of PER2 in the BLA resulting in significantly lower expression at ZT 0 for the TMT0 group and significantly higher expression at ZT 6 and ZT 12 for both experimental groups (A). TMT exposure also resulted in an increase of c-Fos expression at ZT 0 for both groups, with the increase for the TMT0 group significantly higher than the TMT12 group (B). Photomicrographs showing low amount of PER2 immunoreactivity in the BLA of a TMT 0 animal at ZT 0 (C) and normal amount of immunoreactivity the same timepoint for a TMT12 animal (D). Photomicrographs showing increased c-Fos expression at ZT 0 in the BLA of a TMT0 animal (E) and lower level of expression at ZT 0 in a TMT12 animal (F). *significantly different from control group at that time point (p<0.05) **significantly different from control and experimental group at that timepoint (p<0.05). The values for ZT 0 are repeated as ZT 24. Error bars represent standard errors.
Mentions: Repeated exposure to TMT at ZT 0 essentially reversed the normal rhythm of PER2 expression in the BLA (Figure 3 A, C & D, Table 1) with a peak of expression occurring at ZT 6 and the lowest point of expression at ZT 0. The amount of PER2-IR was significantly lower than control mice at ZT 0, and significantly higher than control mice at ZT 6 and ZT 12 (Figure 3 A). In comparison, results for the TMT12 group were different. PER2 in the TMT12 group remained at control levels in the BLA at ZT 0 and ZT 18 but did not have the normal decrease in PER2 expression at ZT 6 and ZT12, which resulted in essence, a lack of rhythmic PER2 expression, with expression remaining relatively high at all timepoints. (Figure 3, Table 1). The amount of PER2-IR was significantly higher at ZT 0 compared to the TMT0 group, and significantly higher at ZT 6 and ZT 12 compared to the control group (Figure 3 A). Changes in PER2 expression in response to TMT exposure were accompanied by increased c-Fos expression only at ZT 0 for both experimental groups, with the increase in the TMT0 group significantly greater than both the control and TMT12 groups (Figure 3 B). The rhythm of c-Fos expression in the BLA however was not affected by TMT exposure (Table 2).

Bottom Line: These changes were accompanied by increased c-Fos expression at ZT0.In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group.The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Northeastern University, Boston, Massachusetts, United States of America. hantazo@mclean.harvard.edu

ABSTRACT
Evidence demonstrates that rodents learn to associate a foot shock with time of day, indicating the formation of a fear related time-stamp memory, even in the absence of a functioning SCN. In addition, mice acquire and retain fear memory better during the early day compared to the early night. This type of memory may be regulated by circadian pacemakers outside of the SCN. As a first step in testing the hypothesis that clock genes are involved in the formation of a time-stamp fear memory, we exposed one group of mice to fox feces derived odor (TMT) at ZT 0 and one group at ZT 12 for 4 successive days. A separate group with no exposure to TMT was also included as a control. Animals were sacrificed one day after the last exposure to TMT, and PER2 and c-Fos protein were quantified in the SCN, amygdala, hippocampus, and piriform cortex. Exposure to TMT had a strong effect at ZT 0, decreasing PER2 expression at this time point in most regions except the SCN, and reversing the normal rhythm of PER2 expression in the amygdala and piriform cortex. These changes were accompanied by increased c-Fos expression at ZT0. In contrast, exposure to TMT at ZT 12 abolished the rhythm of PER2 expression in the amygdala. In addition, increased c-Fos expression at ZT 12 was only detected in the central nucleus of the amygdala in the TMT12 group. TMT exposure at either time point did not affect PER2 or c-Fos in the SCN, indicating that under a light-dark cycle, the SCN rhythm is stable in the presence of repeated exposure to a fear-inducing stimulus. Taken together, these results indicate that entrainment to a fear-inducing stimulus leads to changes in PER2 and c-Fos expression that are detected 24 hours following the last exposure to TMT, indicating entrainment of endogenous oscillators in these regions. The observed effects on PER2 expression and c-Fos were stronger during the early day than during the early night, possibly to prepare appropriate systems at ZT 0 to respond to a fear-inducing stimulus.

Show MeSH
Related in: MedlinePlus