Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system

Abstract

Circadian rhythms regulate most physiological processes. Adjustments to circadian time, called phase shifts, are necessary following international travel and on a more frequent basis for individuals who work non-traditional schedules such as rotating shifts. As the disruption that results from frequent phase shifts is deleterious to both animals and humans, we sought to better understand the kinetics of resynchronization of the mouse circadian system to one of the most disruptive phase shifts, a 6-h phase advance. Mice bearing a luciferase reporter gene for mPer2 were subjected to a 6-h advance of the light cycle and molecular rhythms in suprachiasmatic nuclei (SCN), thymus, spleen, lung and esophagus were measured periodically for 2 weeks following the shift. For the SCN, the master pacemaker in the brain, we employed high-resolution imaging of the brain slice to describe the resynchronization of rhythms in single SCN neurons during adjustment to the new light cycle. We observed significant differences in shifting kinetics among mice, among organs such as the spleen and lung, and importantly among neurons in the SCN. The phase distribution among all Period2-expressing SCN neurons widened on the day following a shift of the light cycle, which was partially due to cells in the ventral SCN exhibiting a larger initial phase shift than cells in the dorsal SCN. There was no clear delineation of ventral and dorsal regions, however, as the SCN appear to have a population of fast-shifting cells whose anatomical distribution is organized in a ventral-dorsal gradient. Full resynchronization of the SCN and peripheral timing system, as measured by a circadian reporter gene, did not occur until after 8 days in the advanced light cycle.

Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag

“…Yamazaki et al have found that during jet lag, Per1 expression rhythms reentrain faster in the SCN than in any of the other tissues examined (22). Similar findings were reported by Davidson et al for Per2 (31). Reddy et al found a dissociation of period and cryptochrome gene expression rhythms during jet lag and postulated that the slower-adapting cryptochrome rhythm acts as a rate-limiting factor for behavioral adaptation (32).…”

“…Using a short day protocol, we defined day 1 as the first advanced dark period (similar to Davidson et al, who used a short night approach in which the first day is defined by the deemed light period; ref. 31; but different from Yamazaki et al, where the following day -corresponding to day 2 in our study -was referred to as day 1; ref. 22).…”

“…Reddy and colleagues provide evidence that cryptochrome rhythm entrainment closely correlates with that of behavior (32). Another aspect of perturbation was shown within the SCN itself, where cells can be separated in ventral and dorsal regions that show different resetting kinetics during the period of desynchrony (31).…”

Neural correlates of individual differences in circadian behaviour

“…Briefly, mice were sacrificed at ZT7 -10, which does not reset the SCN [25,26]. Brains were sectioned in the coronal plane and three consecutive slices (150 mm) were retained from the rostral, middle and caudal portions of the SCN (figure 1c).…”

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

“…Similarly, peripheral oscillators across tissues and organs also need to resynchronize with each other and the SCN, and generally take longer to resynchronize than the SCN (Yamazaki et al 2000). However, the length of time necessary to achieve stable phases attuned to the new photoperiod varies between tissues and organs (for review, see Harrington 2010), with 8 d necessary for full peripheral resynchronization following a 6 h phase advance (Davidson et al 2009;Kiessling et al 2010). Throughout the last two centuries, technological advances have dramatically changed individual work and rest patterns.…”