Journal of Biological Rhythms

Threads of evidence from recent experimentation in retinal morphology, neurochemistry, electrophysiology, and visual perception point toward rhythmic ocular processes that may be integral components of circadian entrainment in mammals. Components of retinal cell biology (rod outer- segment disk shedding, inner-segment degradation, melatonin and dopamine synthesis, electrophysiological responses) show self-sustaining circadian oscillations whose phase can be controlled by light-dark cycles. A complete phase response curve in visual sensitivity can be generated from light-pulse-induced phase shifting. Following lesions of the suprachiasmatic nuclei, circadian rhythms of visual detectability and rod outer-segment disk shedding persist, even though behavioral activity becomes arrhythmic. We discuss the converging evidence for an ocular circadian timing system in terms of interactions between rhythmic retinal processes and the central suprachiasmatic pacemaker, and propose that retinal phase shifts to light provide a critical input signal.

Acute light pulses as well as long-term light exposure may not only modulate photoreceptive properties, but also induce reversible or irreversible damage to the retina, depending on exposure conditions. Illuminance levels in laboratory animal colonies and manipulations of lighting regimens in circadian rhythm research can threaten retinal structure and physiology, and may therefore modify zeitgeber input to the central circadian system. Given the opportunity to escape light at any time, the nocturnal rat self-selects a seasonally varying "naturalistic skeleton photoperiod" that protects the eyes from potential damage by nonphysiological light exposures. Both rod outer-segment disk shedding and behavioral circadian phase shifts are elicited by low levels of twilight stimulation. From this vantage point, we hypothesize that certain basic properties of circadian rhythms (e.g., Aschoff's rule and splitting) may reflect modulation of retinal physiology by light. Pharmacological manipulations with or without the addition of lighting strategies have been used to analyze the neurochemistry of circadian timekeeping. Drug modulation of light input at the level of the retina may add to or interact with direct drug modulation of the central circadian pacemaking system.

Individually identified, 2-year-old female rainbow trout were maintained for up to 51 months on a constant schedule of 6 hr light and 18 hr darkness (LD 6:18), constant temperature (8.5-9.0°C), and constant feeding rate. The fish exhibited free-running circannual rhythms of gonadal maturation and ovulation, which were self-sustaining for up to three cycles. The periodicity of the rhythm showed variation between fish and in successive cycles for the same fish, ranging from approximately 11 to 15 months.

Long-term extracellular recordings from a spiking, movement-sensitive giant neuron (H1) in the third optic ganglion of the blowfly Calliphora vicina (L.) revealed periodic endogenous sensitivity fluctuations. The sensitivity changes showed properties typical of an endogenous circadian rhythm. This was true for the responses in reaction to intensity changes of visual patterns as well as for the responses elicited by pattern movement. For these two types of stimuli, the circadian fluctuations were comparable, but the envelope in the case of responses to movement was more robust. A circadian fluctuation in responses to movement is, therefore, present at the level of single elementary movement detectors.

The tonic activity of the neuron was also shown to be under circadian control. In constant darkness (DD) the fluctuation was circadian, whereas in constant light it was not. The subjective light-dark (LD) transitions in the tonic activity in DD closely followed the LD transitions in the holding cages initially; that is, there was low activity at night and high activity during the daytime. The sensitivity fluctuations in response to visual stimuli led the tonic spike activity fluctuations by several hours.

Circadian rhythms of hamsters can be phase-shifted or entrained by single or daily sessions of induced wheel running. In contrast, observations of rats under restricted-feeding schedules suggest that their free-running rhythms are not readily entrainable by a daily bout of intense activity. A formal test of this idea was made by subjecting rats to daily 2-hr or 3-hr sessions of forced treadmill activity. None of 18 rats entrained to a daily treadmill schedule when tested in constant dim light, but 1 of 16 did entrain when tested after blinding, when the period of its free-running activity rhythm was very close to the period of the treadmill schedule and when the onset of its daily active phase overlapped with the treadmill sessions. These conditions were recreated in a final group of eight rats; the rats were trained in a light-dark cycle, blinded, and subjected to a treadmill schedule with a period of 23.91 hr that was initiated at the onset of the rats' active phase on day 1. Six of these rats entrained. The mechanism for entrainment by activity schedules clearly exists in rats, but the conditions under which this occurs are highly constrained, suggesting that activity is a very weak zeitgeber in this species. It is argued that the evolution of functionally separable food- and light-entrainable oscillators in the rat demands a very low sensitivity to feedback effects of activity.

Simulated time zone transitions were performed in an isolation unit upon groups of one to four human subjects. In the first series of experiments, the adjustment of the circadian rhythm of body temperature, measured in the presence of sleep and other masking factors, was assessed by cosinor analysis and by cross-correlation methods. These methods modeled the circadian timing system either as a single component or as the sum of two components, those due to exogenous and endogenous influences. The one-component models described a more rapid adjustment of the temperature rhythm to the time zone transition than did the two-component models; we attribute this difference to the masking effects of the exogenous component. In a second series of experiments, we showed that the shift of the endogenous component, as assessed by the two-component models, was not significantly different from that measured during constant routines. The results also showed that, if the zeitgebers were phased in advance of the endogenous component, then advances of the endogenous component were produced only if this mismatch was less than about 10 hr. Mismatches greater than this, and cases where the zeitgebers were delayed with respect to the endogenous component, both produced delays of the endogenous component. We conclude that the two-component cross-correlation methods can be used to estimate shifts of the endogenous component of a circadian rhythm in the presence of masking factors. They are therefore an alternative to constant routines when these latter are impracticable to carry out.