Distinct patterns of Period gene expression in the suprachiasmatic nucleus underlie circadian clock photoentrainment by advances or delays

Abstract

The circadian clock in the mammalian hypothalamic suprachiasmatic nucleus (SCN) is entrained by the ambient light/dark cycle, which differentially acts to cause the clock to advance or delay. Light-induced changes in the rhythmic expression of SCN clock genes are believed to be a critical step in this process, but how the two entrainment modalities-advances vs. delays-engage the molecular clockwork remains incompletely understood. We investigated molecular substrates of photic entrainment of the clock in the SCN by stably entraining hamsters to T cycles (non-24-h light/ dark cycles) consisting of a single 1-h light pulse repeated as either a short (23.33-h) or a long (24.67-h) cycle; under these conditions, the light pulse of the short cycle acts as "dawn," whereas that of the long cycle acts as "dusk." Analyses of the expression of the photoinducible and rhythmic clock genes Period 1 and 2 (Per1 and Per2) in the SCN revealed fundamental differences under these two entrainment modes. Light at dawn advanced the clock, advancing the onset of the Per1 mRNA rhythm and acutely increasing mRNA transcription, whereas light at dusk delayed the clock, delaying the offset of the Per2 mRNA rhythm and tonically increasing mRNA stability. The results suggest that the underlying molecular mechanisms of circadian entrainment differ with morning (advancing) or evening (delaying) light exposure, and such differences may reflect how entrainment takes place in nocturnal animals under natural conditions. circadian synchronization | circadian clock resetting | light entrainment A fundamental feature of the circadian clock that regulates daily behavioral and physiological rhythmicity is its entrainment to the environmental cycle of light and darkness. By matching the clock's endogenous ("free-running") period to that of the ambient day/night cycle, entrainment ensures that the phase relationship between clock and external day remains stable over time, thereby synchronizing body rhythms to local time. Light is the clock's preeminent entraining cue (Zeitgeber), and the clock responds to light by changing its angular velocity and shifting its phase. To match its oscillation to that of the Zeitgeber, the clock can increase its velocity and advance its phase if the clock's freerunning period is too long, or it can decrease its velocity and delay its phase if its free-running period is too short (1, 2).In mammals, the master circadian clock is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus (3). The SCN is composed of multiple, coupled single-cell circadian oscillators (4), and analyses of induced and spontaneous mutations, gene sequence homologies, and protein-protein interactions have identified candidate regulatory molecules and biochemical processes that are likely to constitute the basic intracellular oscillatory mechanism (5). Genes at the core of the clock function within autoregulatory feedback loops, with proteins rhythmically suppressing the transcription of their own mRNAs. When the basic helix-loop-hel...

Circadian gene expression in peripheral blood leukocytes of rotating night shift nurses

“…It is widely known that resetting of the peripheral clocks can occur through regulation of the expression of clock genes caused by internal or external cues. Generally, light exposure in the morning advances and light exposure in the evening delays circadian systems in organisms, which may cause serious effects due to irregular and disturbed wake-sleep cycle of humans (26). It was found that shift work caused a delay of the clock gene's acrophase in human peripheral tissues.…”

Effects of Circadian Disruption on Physiology and Pathology: From Bench to Clinic (and Back)

“…LD Cycles Outside the Range of Entrainment LD cycles with a T period (i.e., T cycles) can be experimentally set outside the entrainment limits, where the τ − T difference is not normally compensated with a given phase-relationship (Plano et al 2010;Schwartz et al 2011). Classical experiments in humans used these T-cycle protocols in order to evidence endogenous circadian regulation (Aschoff and Wever 1981).…”

Optimal Implementations for Reliable Circadian Clocks

“…In hamsters, Schwartz et al [15] reported different gene expressions of Per1 and Per2 when entrained by two types of periodic light pulses that have short (23.33 h) and long (24.67 h) periods. Let us reproduce Schwartz's experiment in our optimization framework with two inputs.…”

“…At the behavioral level, we rationalize a time period during which the time is neither advanced nor delayed by light in an optimal clock [14]. Our theory can also explain different gene expression patterns when entrained by two different light pulses [15]. In this study we investigate the optimal implementations for multiple input pathways to achieve the maximal limit of entrainability and regularity.…”

“…We again set α ¼ 1 and ν ¼ 1.47 and assume x j 1 ¼ ½Per1 and x j 2 ¼ ½Per2. Reference [15] applied a periodic light pulse of 1 h duration, which we modeled with a periodic δ function,…”