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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 PER2 expression and induces a rhythm in c-Fos expression in the Piriform Cortex (PirCx).TMT exposure increased the amount of PER2 expression at ZT 0 for the TMT12 group and at ZT 6 and ZT 12 for both experimental groups in the PirCx (A). Expression of c-Fos was increased at ZT 0 and ZT 12 for both experimental groups, with the increase at ZT 12 for the TMT0 group significantly greater than the TMT12 group (B). Photomicrographs showing normal level of PER2 expression in the PirCx of a TMT0 animal at ZT 0 (C) and higher level of expression at the same timepoint in a TMT12 animal (D). Photomicrographs showing high level of expression of c-Fos at ZT 0 for a TMT0 animal (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-g006: TMT exposure alters PER2 expression and induces a rhythm in c-Fos expression in the Piriform Cortex (PirCx).TMT exposure increased the amount of PER2 expression at ZT 0 for the TMT12 group and at ZT 6 and ZT 12 for both experimental groups in the PirCx (A). Expression of c-Fos was increased at ZT 0 and ZT 12 for both experimental groups, with the increase at ZT 12 for the TMT0 group significantly greater than the TMT12 group (B). Photomicrographs showing normal level of PER2 expression in the PirCx of a TMT0 animal at ZT 0 (C) and higher level of expression at the same timepoint in a TMT12 animal (D). Photomicrographs showing high level of expression of c-Fos at ZT 0 for a TMT0 animal (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: In contrast to other brain regions, TMT exposure did not decrease PER2 expression at ZT 0 in the TMT0 group. Instead, TMT exposure resulted in significant increase of PER2 expression at ZT 6 and ZT 12 in the TMT0 group compared to control mice (Figure 6 A, C & D). This resulted in rhythmic PER2 expression that is somewhat anti-phase to control animals (Figure 6A, Table 1). In the TMT12 group, TMT exposure resulted in significantly increased PER2 expression at every time point except for ZT 18 when compared to control animals (Figure 6). Although there was no significant rhythm in c-Fos expression in control mice (Figure 6B, Table 2), TMT exposure resulted in an induction of rhythmic c-Fos expression in both experimental groups (Figure 6B, Table 2). The amount of c-Fos expression was significantly increased at ZT0 and ZT12 in both groups in comparison to the control group (Figure 6B, E & F). C-Fos expression at ZT 12 was also significantly increased in the TMT0 group when compared to the TMT12 group (Figure 6B).


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 PER2 expression and induces a rhythm in c-Fos expression in the Piriform Cortex (PirCx).TMT exposure increased the amount of PER2 expression at ZT 0 for the TMT12 group and at ZT 6 and ZT 12 for both experimental groups in the PirCx (A). Expression of c-Fos was increased at ZT 0 and ZT 12 for both experimental groups, with the increase at ZT 12 for the TMT0 group significantly greater than the TMT12 group (B). Photomicrographs showing normal level of PER2 expression in the PirCx of a TMT0 animal at ZT 0 (C) and higher level of expression at the same timepoint in a TMT12 animal (D). Photomicrographs showing high level of expression of c-Fos at ZT 0 for a TMT0 animal (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-g006: TMT exposure alters PER2 expression and induces a rhythm in c-Fos expression in the Piriform Cortex (PirCx).TMT exposure increased the amount of PER2 expression at ZT 0 for the TMT12 group and at ZT 6 and ZT 12 for both experimental groups in the PirCx (A). Expression of c-Fos was increased at ZT 0 and ZT 12 for both experimental groups, with the increase at ZT 12 for the TMT0 group significantly greater than the TMT12 group (B). Photomicrographs showing normal level of PER2 expression in the PirCx of a TMT0 animal at ZT 0 (C) and higher level of expression at the same timepoint in a TMT12 animal (D). Photomicrographs showing high level of expression of c-Fos at ZT 0 for a TMT0 animal (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: In contrast to other brain regions, TMT exposure did not decrease PER2 expression at ZT 0 in the TMT0 group. Instead, TMT exposure resulted in significant increase of PER2 expression at ZT 6 and ZT 12 in the TMT0 group compared to control mice (Figure 6 A, C & D). This resulted in rhythmic PER2 expression that is somewhat anti-phase to control animals (Figure 6A, Table 1). In the TMT12 group, TMT exposure resulted in significantly increased PER2 expression at every time point except for ZT 18 when compared to control animals (Figure 6). Although there was no significant rhythm in c-Fos expression in control mice (Figure 6B, Table 2), TMT exposure resulted in an induction of rhythmic c-Fos expression in both experimental groups (Figure 6B, Table 2). The amount of c-Fos expression was significantly increased at ZT0 and ZT12 in both groups in comparison to the control group (Figure 6B, E & F). C-Fos expression at ZT 12 was also significantly increased in the TMT0 group when compared to the TMT12 group (Figure 6B).

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