Circadian system of mice integrates brief light stimuli

Abstract

Light is the primary sensory stimulus that synchronizes or entrains the internal circadian rhythms of animals to the solar day. In mammals photic entrainment of the circadian pacemaker residing in the suprachiasmatic nuclei is due to the fact that light at certain times of day can phase shift the pacemaker. In this study we show that the circadian system of mice can integrate extremely brief, repeated photic stimuli to produce large phase shifts. A train of 2-ms light pulses delivered as one pulse every 5 or 60 s, with a total light duration of 120 ms, can cause phase shifts of several hours that endure for weeks. Single 2-ms pulses of light were ineffective. Thus these data reveal a property of the mammalian circadian clock: it can integrate and store latent sensory information in such a way that a series of extremely brief photic stimuli, each too small to cause a phase shift individually, together can cause a large and long-lasting change in behavior.

Circadian phase resetting by a single short-duration light exposure

“…The rate of decline from the prompt to the sustained drive follows a nonlinear pattern. Our results in humans are consistent with results from animal studies that showed light-induced phase resetting to be most efficient at the beginning of the LE, with minimal additional phase shift produced by further extension of the light stimulus due to a reduction in photic responsiveness of the circadian pacemaker (3,4,8,13). A recent report documents that the number of light-evoked action potentials per photon from intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate LE-induced phase shifts declines as the duration of the photic stimulus increases (14).…”

“…More recently, a train of sixty 2-millisecond pulses administered every minute over 60 minutes induced ~45 minutes of phase delay (6,7). Given that the circadian pacemaker can integrate photic signals (3,8), these multiple-exposure studies cannot isolate the phase shift induced by each individual pulse. Mechanistic studies of phase resetting in animals show that the pacemaker can integrate and respond to pulses presented 60 minutes apart (17) and that the majority of a phase-resetting response occurs at the beginning of the light pulse (18)(19)(20).…”

“…Initial studies examining the phase-resetting effects of light used long-duration (5 hours) and high-intensity (~9,500 lux) light (2) because the human circadian system was thought to be less sensitive to light than that of other mammals. While the circadian pacemaker in mice (3), rats (4), hamsters (5), and humans (6, 7) is known to respond to a sequence of millisecond flashes (administered over 5 seconds in rats, over 5-60 minutes in mice and hamsters, and over 60 minutes in humans), a single millisecond flash does not reset the mammalian pacemaker at the intensities that have been tested (3,8), suggesting that circadian resetting requires integration of the photic signal over a longer exposure interval.A nonlinear relationship exists between light exposure (LE) duration and the magnitude of circadian phase resetting responses. A single 12-minute pulse of light can shift the human pacemaker 8 times more BACKGROUND.…”

Temporal integration of light flashes by the human circadian system

“…Shorter duration of light exposures in the order of microseconds to milliseconds have been tested in rodents (45)(46)(47). While a single 2-millisecond flash of light is insufficient to phase shift the murine circadian system, a sequence of flashes administered once per minute for 60 minutes is sufficient to evoke phase delays (48). This study by Van Den Pol and colleagues, in addition to other published studies in rodents (45)(46)(47), established that the mammalian circadian system has the capacity to respond to a sequence of very brief, millisecond flashes of light.…”

Intrinsically photosensitive retinal ganglion cells

“…It should be noted, however, that brief (1 s) light pulses (DeCoursey 1972;Earnest and Turek 1983) or a short series of extremely brief (2 ms), intense light flashes, which are ineffective as single flashes (van den Pol et al 1998;Vidal and Morin 2007) can produce significant phase shifts of the circadian clock. Very brief stimuli do not appear to demonstrate the same type of temporal integration associated with light pulses several minutes in duration (Nelson and Takahashi 1999;Vidal and Morin 2007;Morin et al 2010).…”