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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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PER2 and c-Fos in the hippocampus is minimally affected by TMT exposure.TMT exposure resulted in overall higher expression of PER2 for both experimental groups, with the exception of lower expression at ZT 0 for the TMT0 group (A). In contrast, c-Fos expression in the Hipp is not affected by TMT exposure (B). Photomicrographs showing less PER2 immunoreactivity at ZT 0 in the Hipp of a TMT0 animal (C) and high amount of immunoreactivity in the Hipp of a TMT12 animal (D). Photomicrographs showing similar amount of c-Fos immunoreactivity in the Hipp of a TMT0 (E) and 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-g005: PER2 and c-Fos in the hippocampus is minimally affected by TMT exposure.TMT exposure resulted in overall higher expression of PER2 for both experimental groups, with the exception of lower expression at ZT 0 for the TMT0 group (A). In contrast, c-Fos expression in the Hipp is not affected by TMT exposure (B). Photomicrographs showing less PER2 immunoreactivity at ZT 0 in the Hipp of a TMT0 animal (C) and high amount of immunoreactivity in the Hipp of a TMT12 animal (D). Photomicrographs showing similar amount of c-Fos immunoreactivity in the Hipp of a TMT0 (E) and 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 effects of TMT exposure in the BLA and CE, PER2 expression in the Hipp of the TMT0 group was significantly decreased at ZT 0 but significantly increased at ZT 6 compared to control subjects (Figure 5 A, C & D). PER2 expression was still rhythmic in the TMT0 group (Table 1). Unlike the BLA and CE, PER2 expression in the Hipp of the TMT12 group was still rhythmic (Table 1). The amount of PER2 expression however was significantly higher in the TMT12 group compared to the control group at every timepoint except for ZT 12 (Figure 5). The rhythm and amount of c-Fos expression were not affected in the Hipp of either experimental group in comparison to the control mice (Figure 5 B, 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)

PER2 and c-Fos in the hippocampus is minimally affected by TMT exposure.TMT exposure resulted in overall higher expression of PER2 for both experimental groups, with the exception of lower expression at ZT 0 for the TMT0 group (A). In contrast, c-Fos expression in the Hipp is not affected by TMT exposure (B). Photomicrographs showing less PER2 immunoreactivity at ZT 0 in the Hipp of a TMT0 animal (C) and high amount of immunoreactivity in the Hipp of a TMT12 animal (D). Photomicrographs showing similar amount of c-Fos immunoreactivity in the Hipp of a TMT0 (E) and 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

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getmorefigures.php?uid=PMC3105109&req=5

pone-0020658-g005: PER2 and c-Fos in the hippocampus is minimally affected by TMT exposure.TMT exposure resulted in overall higher expression of PER2 for both experimental groups, with the exception of lower expression at ZT 0 for the TMT0 group (A). In contrast, c-Fos expression in the Hipp is not affected by TMT exposure (B). Photomicrographs showing less PER2 immunoreactivity at ZT 0 in the Hipp of a TMT0 animal (C) and high amount of immunoreactivity in the Hipp of a TMT12 animal (D). Photomicrographs showing similar amount of c-Fos immunoreactivity in the Hipp of a TMT0 (E) and 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 effects of TMT exposure in the BLA and CE, PER2 expression in the Hipp of the TMT0 group was significantly decreased at ZT 0 but significantly increased at ZT 6 compared to control subjects (Figure 5 A, C & D). PER2 expression was still rhythmic in the TMT0 group (Table 1). Unlike the BLA and CE, PER2 expression in the Hipp of the TMT12 group was still rhythmic (Table 1). The amount of PER2 expression however was significantly higher in the TMT12 group compared to the control group at every timepoint except for ZT 12 (Figure 5). The rhythm and amount of c-Fos expression were not affected in the Hipp of either experimental group in comparison to the control mice (Figure 5 B, 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