Daily performance of a sustained attention task during light phase desynchronizes circadian oscillators in nocturnal rats.

Previous studies demonstrated that daily performance of a sustained attention task (SAT) for water reward during the light phase causes nocturnal rats to entrain to a diurnal activity pattern (Gritton et al., 2009). In addition, level of performance during the light phase was significantly lowered when compared to dark phase performance. We hypothesized that the shift to a diurnal activity pattern observed in animals trained during the light phase was due to desynchronization of the SCN and peripheral oscillators. To test this hypothesis, SAT practice occurred either during the light phase at ZT4 [SAT4] or during the dark phase at ZT16 [SAT16]. A control group practiced a daily fixed interval 9 s [FI-9] schedule of reinforcement at ZT4. Light/dark cycle was 12:12 and food was provided ad libitum. A second control group was handled at randomly selected times but was neither water-deprived nor performed [NP]. Circadian behavioral activity was recorded to verify the SAT effect on circadian rhythm. As circadian clock operates in most tissues via transcriptional feedback that involve the products of circadian clock genes, we hypothesized that expression of the clock genes present in the gastrointestinal tract (Hoogerwerf et al., 2007) were altered in SAT4 animals. Preliminary data show that SAT4 animals have dampened Period2 (Per2) rhythms in the colon when compared to FI-9 and NP animals. Results from ongoing experiments indicate that Per2 expression in the SCN is not altered by SAT4 practice; however, in non-SCN areas in the brain Per2 expression is attenuated. To better understanding the relationship between the SCN and the peripheral oscillators, additional biopsy data was collected from the heart, lung, liver, kidney, and stomach at 4 time points (ZT2, ZT8, ZT14, and ZT20). As circadian misalignment is associated with diabetes, obesity and metabolic syndrome, food intake and stool output of SAT4, SAT16, FI-9 and NP animals were collected. SAT4 animals’ food intake was significantly higher compared to NP and their gastrointestinal motility was altered as well. Furthermore, preliminary corticosterone data suggests that day/night differences are attenuated in SAT4 animals as compared to SAT16 animals, and SAT trained animals have overall elevated corticosterone levels compared to NP animals. This research provides new insights in understanding cognitive work-induced shifts in circadian rhythms, the cause and role of circadian abnormalities in neuropsychiatric disorders, obesity and metabolic syndrome, and it eventually will inform the development of treatments of such disorders.