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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 differentially affects PER2 and c-Fos in the central amygdala (CE) based on time of exposure.TMT exposure altered the rhythm and amount of PER2 expression in the CE amygdala of both groups, resulting in a low level of expression at ZT0 in the TMT0 group, followed by a high level of expression at ZT 6 for both groups, and a low level of expression at ZT 18 for both groups (A). TMT resulted in increased c-Fos expression at ZT 0 only for the TMT0 group, and increased expression at ZT 12 only for the TMT12 group (B). Photomicrographs showing decreased PER2 immunoreactivity in the CE of a TMT0 animal at ZT 0 (C) in comparison to a TMT12 animal (D). Photomicrographs depicting increased c-Fos expression at ZT 0 for a TMT0 animal (E) in comparison to 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-g004: TMT exposure differentially affects PER2 and c-Fos in the central amygdala (CE) based on time of exposure.TMT exposure altered the rhythm and amount of PER2 expression in the CE amygdala of both groups, resulting in a low level of expression at ZT0 in the TMT0 group, followed by a high level of expression at ZT 6 for both groups, and a low level of expression at ZT 18 for both groups (A). TMT resulted in increased c-Fos expression at ZT 0 only for the TMT0 group, and increased expression at ZT 12 only for the TMT12 group (B). Photomicrographs showing decreased PER2 immunoreactivity in the CE of a TMT0 animal at ZT 0 (C) in comparison to a TMT12 animal (D). Photomicrographs depicting increased c-Fos expression at ZT 0 for a TMT0 animal (E) in comparison to 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: Similar to the BLA, exposure to TMT reversed the normal rhythm of PER2 expression in the CE of the TMT0 group, with a peak of PER2 expression occurring at ZT 6 and the low point occurring at ZT 0, with significantly lower PER2-IR than both the control and TMT12 group at ZT 0 (Figure 4 A, C & D, Table 1). Results for the TMT12 group in the CE were similar to results observed in the BLA, with a loss of rhythm in PER2 expression and significantly lower expression at ZT 0 when compared to controls (Figure 4 A, Table 1). Also similar to results in the BLA, c-Fos expression in the TMT0 group was significantly increased only at ZT 0 compared to both control and TMT12 mice, but the rhythm in c-Fos expression was not affected in the TMT0 group (Figure 4, Table 2). In contrast to the effect of c-Fos observed in the BLA, c-Fos expression in the TMT12 group was not increased at ZT 0, it was however significantly increased at ZT 12 compared to both the control and TMT0 groups (Figure 4 B).


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 differentially affects PER2 and c-Fos in the central amygdala (CE) based on time of exposure.TMT exposure altered the rhythm and amount of PER2 expression in the CE amygdala of both groups, resulting in a low level of expression at ZT0 in the TMT0 group, followed by a high level of expression at ZT 6 for both groups, and a low level of expression at ZT 18 for both groups (A). TMT resulted in increased c-Fos expression at ZT 0 only for the TMT0 group, and increased expression at ZT 12 only for the TMT12 group (B). Photomicrographs showing decreased PER2 immunoreactivity in the CE of a TMT0 animal at ZT 0 (C) in comparison to a TMT12 animal (D). Photomicrographs depicting increased c-Fos expression at ZT 0 for a TMT0 animal (E) in comparison to 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.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105109&req=5

pone-0020658-g004: TMT exposure differentially affects PER2 and c-Fos in the central amygdala (CE) based on time of exposure.TMT exposure altered the rhythm and amount of PER2 expression in the CE amygdala of both groups, resulting in a low level of expression at ZT0 in the TMT0 group, followed by a high level of expression at ZT 6 for both groups, and a low level of expression at ZT 18 for both groups (A). TMT resulted in increased c-Fos expression at ZT 0 only for the TMT0 group, and increased expression at ZT 12 only for the TMT12 group (B). Photomicrographs showing decreased PER2 immunoreactivity in the CE of a TMT0 animal at ZT 0 (C) in comparison to a TMT12 animal (D). Photomicrographs depicting increased c-Fos expression at ZT 0 for a TMT0 animal (E) in comparison to 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: Similar to the BLA, exposure to TMT reversed the normal rhythm of PER2 expression in the CE of the TMT0 group, with a peak of PER2 expression occurring at ZT 6 and the low point occurring at ZT 0, with significantly lower PER2-IR than both the control and TMT12 group at ZT 0 (Figure 4 A, C & D, Table 1). Results for the TMT12 group in the CE were similar to results observed in the BLA, with a loss of rhythm in PER2 expression and significantly lower expression at ZT 0 when compared to controls (Figure 4 A, Table 1). Also similar to results in the BLA, c-Fos expression in the TMT0 group was significantly increased only at ZT 0 compared to both control and TMT12 mice, but the rhythm in c-Fos expression was not affected in the TMT0 group (Figure 4, Table 2). In contrast to the effect of c-Fos observed in the BLA, c-Fos expression in the TMT12 group was not increased at ZT 0, it was however significantly increased at ZT 12 compared to both the control and TMT0 groups (Figure 4 B).

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