supine) [7, 8], it may also be influenced by the flow of aqueous humor, which is lowest during the night (~1.3 l/min) and highest during the day (~3 l/min) [9]. The amplitude of the pupillary reflex can change over the course of the day [10].

Electroretinogram responses to stroboscopic flashes exhibit a circadian rhythm in the latency to the peak of the b-wave, with increasing latency throughout the night [11]. A circadian rhythm is observed in the electrooculogram produced by tracking moving objects, with maximal peak-to-peak amplitude in the late morning [11]. Performance on visual tasks also exhibits circadian rhythms in both acuity and sensitivity [11–14].

ENTRAINMENT

While circadian oscillations in physiology and behavior are endogenously generated and regulated, they must be synchronized with the external geophysical and biotic cycles to serve an adaptive function. This is accomplished through entrainment, a process by which an external cue exerts period and phase control over a rhythm such that the endogenous period is adjusted to match that of the external environment (i.e., 24 h). The timing of the organism’s rhythms in relation to timing of events in the environment are also adjusted, such that nocturnal organisms are active at night, and diurnal organisms are active during the day. By controlling both the period and phase of the rhythms, entrainment ensures that physiological events occur at the proper times, and that it is possible to anticipate cyclic challenges.

While many cues can provide time information to the circadian system and thus serve as zeitgebers (from the German zeit “time” and geber “giver”), not every cue has an impact on the circadian system in the same manner or to the same degree. Light is the dominant zeitgeber responsible for entrainment of circadian rhythmicity in most organisms. An intact retina and optic nerve are necessary for light to exert control over the mammalian circadian system [15–17] (although one claim to the contrary exists [18]). Light exposure early in the night will delay the phase of rhythms such that they occur later in subsequent cycles. Light exposure late in the night has the opposite effect and will advance the phase of rhythms [19] (Fig. 1). Light during the daytime has little effect on circadian rhythmicity. Through daily delay and advance adjustments, the endogenous circadian pacemaker has its period adjusted such that it equals that of the applied zeitgeber.

Other cues serve as zeitgebers as well. These include dark pulses [20], exercise [21, 22], and sleep deprivation [23]. These nonphotic stimuli produce large phase advances during the midday and small delays late in the night but have little effect during the early night. A common feature of these zeitgebers is that they increase activity or wakefulness at a time of the day when the organism is generally inactive or asleep [23, 24]. While these phase shifts are independent of those produced by light exposure through the retina, there are interactions between the two zeitgeber systems. Exercise during a light pulse attenuates the resulting photic phase shift [25], possibly by inhibiting neurotransmitter release from retinal ganglion cells [25, 26]. Alternatively, housing animals in constant light for a number of days prior to a nonphotic pulse potentiates the resulting phase shift [27].