Driving home from the night shift: a bright light intervention study.

Sleep deprivation (SD) impairs vigilance and increases the risk of driving accidents during the commute home after night work. Bright light (BL) can enhance alertness and cognitive performance. We examined the effects of BL (5600 lux) versus dim light (DL, 35 lux) at the end of a night awake on driving performance. METHODS: Subjects (N = 19, 22.8 ± 4 ya) completed three conditions, counterbalanced for order at >1 week intervals. The two overnight SD conditions began in the lab at usual bedtime. After six hours in DL, subjects were exposed to 45 min BL or continued DL, and then completed a 44 min driving test (two lap circuit) in a high fidelity simulator. In the rested condition, subjects slept at home until habitual wakeup time, were transported to the lab and ∼45 min after wakeup, received BL and then the driving test. RESULTS: Oral temperature decreased while reaction time and sleepiness increased across both SD nights. BL suppressed salivary melatonin but had little or no effect on sleepiness or reaction time. SD markedly increased incidents and accidents. Five subjects (26%) sustained a terminal accident (eg, car flip) in the SD-DL condition, but none did so in the SD-BL or rested-BL conditions. Compared to SD-DL, SD-BL was associated with fewer incidents and accidents overall, and with better performance on the second lap of the circuit on several performance measures. CONCLUSION: BL at the end of a night shift may have potential as a countermeasure to improve driving following night work.

Behavioral and neural correlates of acute and scheduled hunger in C57BL/6 mice.

In rodents, daily feeding schedules induce food anticipatory activity (FAA) rhythms with formal properties suggesting mediation by food-entrained circadian oscillators (FEOs). The search for the neuronal substrate of FEOs responsible for FAA is an active area of research, but studies spanning several decades have yet to identify unequivocally a brain region required for FAA. Variability of results across studies leads to questions about underlying biology versus methodology. Here we describe in C57BL/6 male mice the effects of varying the 'dose' of caloric restriction (0%, 60%, 80%, 110%) on the expression of FAA as measured by a video-based analysis system, and on the induction of c-Fos in brain regions that have been implicated in FAA. We determined that more severe caloric restriction (60%) leads to a faster onset of FAA with increased magnitude. Using the 60% caloric restriction, we found little evidence for unique signatures of neuronal activation in the brains of mice anticipating a daily mealtime compared to mice that were fasted acutely or fed ad-libitum-even in regions such as the dorsomedial and ventrolateral hypothalamus, nucleus accumbens, and cerebellum that have previously been implicated in FAA. These results underscore the importance of feeding schedule parameters in determining quantitative features of FAA in mice, and demonstrate dissociations between behavioral FAA and neural activity in brain areas thought to harbor FEOs or participate in their entrainment or output.

Entrainment of circadian clocks in mammals by arousal and food.

Circadian rhythms in mammals are regulated by a system of endogenous circadian oscillators (clock cells) in the brain and in most peripheral organs and tissues. One group of clock cells in the hypothalamic SCN (suprachiasmatic nuclei) functions as a pacemaker for co-ordinating the timing of oscillators elsewhere in the brain and body. This master clock can be reset and entrained by daily LD (light-dark) cycles and thereby also serves to interface internal with external time, ensuring an appropriate alignment of behavioural and physiological rhythms with the solar day. Two features of the mammalian circadian system provide flexibility in circadian programming to exploit temporal regularities of social stimuli or food availability. One feature is the sensitivity of the SCN pacemaker to behavioural arousal stimulated during the usual sleep period, which can reset its phase and modulate its response to LD stimuli. Neural pathways from the brainstem and thalamus mediate these effects by releasing neurochemicals that inhibit retinal inputs to the SCN clock or that alter clock-gene expression in SCN clock cells. A second feature is the sensitivity of circadian oscillators outside of the SCN to stimuli associated with food intake, which enables animals to uncouple rhythms of behaviour and physiology from LD cycles and align these with predictable daily mealtimes. The location of oscillators necessary for food-entrained behavioural rhythms is not yet certain. Persistence of these rhythms in mice with clock-gene mutations that disable the SCN pacemaker suggests diversity in the molecular basis of light- and food-entrainable clocks.

Phenotyping food entrainment: motion sensors and telemetry are equivalent.

Rats can anticipate a daily meal by entrainment of a circadian timekeeping mechanism that is anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. The dorsomedial nucleus of the hypothalamus (DMH) has been claimed to be critical for the expression of circadian rhythms of food anticipatory activity, but efforts to confirm this finding have so far failed. Failure to confirm that DMH ablation disrupts or eliminates food anticipatory rhythms has been attributed to the use of overhead motion sensors rather than telemetry to measure locomotor activity. To examine the relationship between motion sensor and telemetric measures of locomotor activity, transponders were implanted into the peritoneal cavity of adult male rats, and activity was recorded continuously by both telemetry and infrared motion sensors. Activity counts were approximately 4 fold higher as detected by telemetry, but normalized activity patterns were virtually identical for the two measures during ad-lib food access, 4 h/day food restriction and total food deprivation after food restriction. Overhead motion sensors and telemetry are equivalent measures of food anticipatory activity in rats. Telemetry is an effective tool for continuous recording of body temperature but has no advantages over infrared motion sensors for measuring food anticipatory activity rhythms.

Neural correlates of arousal-induced circadian clock resetting: hypocretin/orexin and the intergeniculate leaflet.

In Syrian hamsters, some procedures for stimulating behavioural arousal (e.g. running in a novel wheel and sleep deprivation by gentle handling with minimal activity) markedly phase-advance circadian rhythms when applied during the middle of the daily rest period, while other arousal procedures do not (e.g. physical restraint, caffeine and modafinil). The neural basis for this differential effect of arousal procedures on clock resetting is unknown. We used c-fos expression as a marker for neuronal activation to determine whether these arousal procedures differentially activate two nonphotic inputs to the circadian system, the thalamic intergeniculate leaflet (IGL; a proposed nonphotic gateway to the circadian clock) and the hypothalamic hypocretin system (which depolarizes arousal-related cell groups throughout the brain and innervates both the IGL and the peri-suprachiasmatic nucleus region). c-FOS in hypocretin-1-immunoreactive neurons, in hypothalamic nonhypocretin neurons and in the IGL was significantly increased by novel wheel running, gentle handling and physical restraint, but only weakly by systemic injections of modafinil (300 mg/kg) or caffeine (75 mg/kg), at doses that are strongly alerting. Spatial analysis revealed few regional differences in the percentage of cells double-labelled for hypocretin-1 and c-FOS following each treatment. These results suggest that activation of hypocretin neurons (as in the restraint condition) is not sufficient to induce phase shifts, and that gating of arousal effects on circadian clock phase may be downstream from the hypocretin system and from IGL neurons activated by these procedures.