| Abstract No.: | B-E2164 |
| Country: | Canada |
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| Title: | UNCOUPLING OF CIRCADIAN OSCILLATORS IN THE BNSTOV AND CEA FROM THE MASTER SCN CLOCK DURING STABLE ENTRAINMENT TO A 26H T-CYCLE |
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| Authors/Affiliations: | 1 Valerie Harbour*; 1 Tammie Quinn; 1 Shimon Amir;
1 Concordia University, Montreal, QC, Canada
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| Content: | The master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus regulates circadian rhythms throughout the brain and periphery. Using immunocytochemistry for the clock protein Period2 (PER2), an essential component of the molecular circadian clock, our lab has found subordinate circadian oscillators in limbic forebrain areas responsible for emotion, motivation, and memory, including the oval nucleus of the bed nucleus of the stria terminalis (BNSTov), central amygdala (CEA), basolateral amygdala (BLA) and dentate gyrus of the hippocampus (DG). It is known that the SCN can be entrained by light cycles longer than the normal 24h light cycle, but little is known about the effect of such exotic light cycles on circadian clocks outside the SCN. We have previously shown that PER2 expression in the SCN stably entrains to a 26h T-cycle (T26; 1h-25h LD), with expression peaking at the beginning of the active phase of the cycle. In contrast, exposure to the T26 cycle for 30 and 60 days (but not 7 or 14 days) affected PER2 expression in the limbic forebrain. Specifically, levels of PER2 expression in the BNSTov and CEA were decreased at their usual peaking time, whereas those in BLA and DG were unaffected and resembled that seen in control rats entrained to a 24h T-cycle (T24; 1h-23h LD).
Objective: A critical question still remaining is whether this disruption in PER2 expression found in the BNSTov and CEA is the result of a blunted (arrhythmic) or shifted PER2 rhythm. In the present experiment we replicated the data for day 30 and 60 and added 2 timepoints in order to assess the rhythm of PER2 expression.
Methods: Male Wistar rats were entrained to either a T24 or T26 cycle for either 30 or 60 days and sacrificed at one of four time points based on running-wheel activity; activity onset, mid-activity, activity offset, or mid-inactivity. Brains were sliced and stained for PER2 immunoreactivity, and the regions previously mentioned were quantified.
Results: The disruption in PER2 levels seen in the initial experiment in the BNSTov and CEA were due to a shift in the PER2 rhythm, and not a blunting of the rhythm. The PER2 rhythm at day 30 shows a clear uncoupling from that of the SCN. At day 60, we see a similar shift in the PER2 rhythm but to a lesser degree. It is possible that after a certain amount of time the system is able to re-adapt itself to its normal rhythm, and what we’re seeing at day 60 is this transition.
Conclusion: These results show that chronic exposure to exotic light cycles can uncouple circadian oscillators in the limbic forebrain from the master SCN clock and suggest that such cycles may be used to study the functional consequences of coupling and uncoupling of brain circadian oscillators. A greater understanding of how chronic time shifts affect the molecular and behavioral aspects of our biological rhythm could potentially lead to the development of treatments for circadian disorders. |
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