Optimization of circadian responses with shorter and shorter millisecond flashes

Recent work suggests that the circadian pacemaker responds optimally to millisecond flashes of light, not continuous light exposure as has been historically believed. It is unclear whether these responses are influenced by the physical characteristics of the pulsing. In the present study, Drosophila ( n = 2199) were stimulated with 8, 16 or 120 ms flashes. For each duration, the energy content of the exposure was systematically varied by changing the pulse irradiance and the number of stimuli delivered over a fixed 15 min administration window (64 protocols surveyed in all). Results showed that per microjoule invested, 8 ms flashes were more effective at resetting the circadian activity rhythm than 16- and 120 ms flashes (i.e. left shift of the dose–response curve, as well as a higher estimated maximal response). These data suggest that the circadian pacemaker's photosensitivity declines within milliseconds of light contact. Further introduction of light beyond a floor of (at least) 8 ms leads to diminishing returns on phase-shifting.

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Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.273.5.r1800 ◽

1997 ◽

Vol 273 (5) ◽

pp. R1800-R1809 ◽

Cited By ~ 30

Author(s):

Megan E. Jewett ◽

David W. Rimmer ◽

Jeanne F. Duffy ◽

Elizabeth B. Klerman ◽

Richard E. Kronauer ◽

...

Keyword(s):

Steady State ◽

Response Curve ◽

Phase Response Curve ◽

Light Exposure ◽

Light Stimulus ◽

Dead Zone ◽

Bright Light ◽

Temperature Minimum ◽

Circadian Pacemaker ◽

Dim Light

Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (∼10,000 lx) stimulus against a background of very dim light (10–15 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a “dead zone” of photic insensitivity and was compared with another three-cycle PRC that had used a background of ∼150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1–2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

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Actigraphy for Assessing Light Effects on Sleep and Circadian Activity Rhythm in Alzheimer's Dementia: A Narrative Review

Current Alzheimer Research ◽

10.2174/1567205016666191010124011 ◽

2020 ◽

Vol 16 (12) ◽

pp. 1084-1107 ◽

Cited By ~ 1

Author(s):

Markus Canazei ◽

Julian Turiaux ◽

Stefan E. Huber ◽

Josef Marksteiner ◽

Ilona Papousek ◽

...

Keyword(s):

Sleep Problems ◽

Light Exposure ◽

Activity Rhythm ◽

Biological Clock ◽

Bright Light ◽

Critical Discussion ◽

Circadian Activity ◽

Wrist Actigraphy ◽

Light Effects ◽

Architectural Lighting

Background: Alzheimer's Disease (AD) is often accompanied by severe sleep problems and circadian rhythm disturbances which may to some extent be attributed to a dysfunction in the biological clock. The 24-h light/dark cycle is the strongest Zeitgeber for the biological clock. People with AD, however, often live in environments with inappropriate photic Zeitgebers. Timed bright light exposure may help to consolidate sleep- and circadian rest/activity rhythm problems in AD, and may be a low-risk alternative to pharmacological treatment. Objective & Method: In the present review, experts from several research disciplines summarized the results of twenty-seven light intervention studies which used wrist actigraphy to measure sleep and circadian activity in AD patients. Results: Taken together, the findings remain inconclusive with regard to beneficial light effects. However, the considered studies varied substantially with respect to the utilized light intervention, study design, and usage of actigraphy. The paper provides a comprehensive critical discussion of these issues. Conclusion: Fusing knowledge across complementary research disciplines has the potential to critically advance our understanding of the biological input of light on health and may contribute to architectural lighting designs in hospitals, as well as our homes and work environments.

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A Comparative-Study of Circadian Activity Patterns of 2 New Guinean Dasyurid Marsupials, Phascolosorex-Dorsalis and Antechinus-Habbema

Australian Journal of Zoology ◽

10.1071/zo9910661 ◽

1991 ◽

Vol 39 (6) ◽

pp. 661 ◽

Cited By ~ 3

Author(s):

PA Woolley ◽

SA Raftopoulos ◽

GJ Coleman ◽

SM Armstrong

Keyword(s):

Ecological Niche ◽

Wheel Running ◽

Activity Rhythm ◽

Activity Patterns ◽

Food Presentation ◽

Circadian Pacemaker ◽

Diurnal Activity ◽

Circadian Activity ◽

Dark Cycle ◽

Feeding Regimen

Five aspects of the circadian activity rhythm (wheel running, feeding, drinking, duration of time in, and visits to, the nest box) were studied for 129 days in two species of New Guinean dasyurid marsupials that co-exist in mid-montane semi-mossforest. When housed under controlled laboratory conditions, Phascolosorex dorsalis exhibited a diurnal activity pattern whereas Antechinus habbema was nocturnal. Manipulation of the feeding regimen and reversal of the 12: 12 light-dark cycle demonstrated that the diurnal activity of P. dorsalis was not due to synchronisation to food presentation but reflected the behavioural output from an endogenous circadian pacemaker. P. dorsalis appears to be unique among dasyurids in its diurnality. Results are interpreted in terms of the ecological niche being a division of time as well as space.

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Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00047.2006 ◽

2006 ◽

Vol 291 (1) ◽

pp. R180-R188 ◽

Cited By ~ 12

Author(s):

Megan E. Knoch ◽

Dustin Siegel ◽

Marilyn J. Duncan ◽

J. David Glass

Keyword(s):

Sleep Deprivation ◽

Phase Response Curve ◽

Light Exposure ◽

Activity Rhythm ◽

Early Morning ◽

Phase Shifting ◽

Constant Light ◽

Phase Advance ◽

Way 100635 ◽

Receptor Phase

Short-term (1–3 days) constant light exposure (brief LL) potentiates nonphotic phase shifting induced by sleep deprivation and serotonin (5-HT) agonist stimulation. The present assessments reveal that exposure to brief LL markedly alters the magnitude and shape of the 5-HT1A,7 receptor agonist, 8-(+)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahyronapthalene (8-OH-DPAT) phase-response curve, facilitating (∼12 h) phase-advance shifts during the early morning when serotonergics have no phase-shifting effect. Brief LL also reduces the threshold for 8-OH-DPAT shifting at midday, evidenced by 5- to 6-h phase-advance shifts elicited by dosages that have no effect without the LL treatment. The brief LL-potentiated phase advances to intraperitoneal 8-OH-DPAT at zeitgeber time 0 (ZT 0) were blocked by the 5-HT1A antagonists, pindolol and WAY 100635, indicating that this shifting is mediated by 5-HT1A receptors. Antagonists with action at 5-HT7 receptors, including ritanserin and metergoline, were without effect. Although autoradiographic analyses of [3H]8-OH-DPAT binding indicate that brief LL does not upregulate suprachiasmatic nucleus (SCN) 5-HT1A receptor binding, intra-SCN microinjection of 8-OH-DPAT at ZT 0 in brief LL-exposed hamsters induced shifts similar to those produced by intraperitoneal injection, suggesting that SCN 5-HT1A receptors mediate potentiated 8-OH-DPAT-induced shifts during the early morning. Lack of shifting by intra-SCN 8-OH-DPAT at ZT 6 or 18 (when intraperitoneal 8-OH-DPAT induces large shifts), further indicates that brief LL-potentiated shifts at these time points are mediated by 5-HT target(s) outside the SCN. Significantly, sleep deprivation-induced phase-advance shifts potentiated by brief LL (∼9 h) at ZT 0 were blocked by pindolol, suggesting that these behavioral shifts could be mediated by the same SCN 5-HT1A receptor phase-resetting pathway as that activated by 8-OH-DPAT treatment.

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Novel phase-shifting effects of GABAA receptor activation in the suprachiasmatic nucleus of a diurnal rodent

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00575.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. R820-R825 ◽

Cited By ~ 29

Author(s):

C. M. Novak ◽

H. E. Albers

Keyword(s):

Suprachiasmatic Nucleus ◽

Activity Rhythm ◽

Receptor Activation ◽

Phase Shifting ◽

Circadian Pacemaker ◽

Pacemaker Cells ◽

Inhibitory Neurotransmitter ◽

Large Phase ◽

Neurochemical Signal

The vast majority of neurons in the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, contain the inhibitory neurotransmitter GABA. Most studies investigating the role of GABA in the SCN have been performed using nocturnal rodents. Activation of GABAA receptors by microinjection of muscimol into the SCN phase advances the circadian activity rhythm of nocturnal rodents, but only during the subjective day. Nonphotic stimuli that reset the circadian pacemaker of nocturnal rodents also produce phase advances during the subjective day. The role of GABA in the SCN of diurnal animals and how it may differ from nocturnal animals is not known. In the studies described here, the GABAA agonist muscimol was microinjected directly into the SCN region of diurnal unstriped Nile grass rats ( Arvicanthis niloticus) at various times in their circadian cycle. The results demonstrate that GABAA receptor activation produces large phase delays during the subjective day in grass rats. Treatment with TTX did not affect the ability of muscimol to induce phase delays, suggesting that muscimol acts directly on pacemaker cells within the SCN. These data suggest that the circadian pacemakers of nocturnal and diurnal animals respond to the most abundant neurochemical signal found in SCN neurons in opposite ways. These findings are the first to demonstrate a fundamental difference in the functioning of circadian pacemaker cells in diurnal and nocturnal animals.

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Electrical stimulation of the anterior optic chiasm mimics the phase shifting effects of light on the circadian activity rhythm of the Syrian hamster

Biological Rhythm Research ◽

10.1080/09291019409360292 ◽

1994 ◽

Vol 25 (2) ◽

pp. 211-213 ◽

Cited By ~ 2

Author(s):

M. J. De Vries ◽

J. A. Treep ◽

J. H. Meijer

Keyword(s):

Electrical Stimulation ◽

Syrian Hamster ◽

Activity Rhythm ◽

Optic Chiasm ◽

Phase Shifting ◽

Circadian Activity ◽

Circadian Activity Rhythm ◽

Stimulation Of

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Continuous light abolishes the maternal entrainment of the circadian activity rhythm of the pups in the field mouse

Cellular and Molecular Life Sciences ◽

10.1007/bf02143591 ◽

1987 ◽

Vol 43 (5) ◽

pp. 576-578 ◽

Cited By ~ 5

Author(s):

N. Viswanathan ◽

M. K. Chandrashekaran

Keyword(s):

Activity Rhythm ◽

Continuous Light ◽

Field Mouse ◽

Circadian Activity ◽

Circadian Activity Rhythm ◽

Maternal Entrainment

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The circadian activity rhythm is reset by nanowatt pulses of ultraviolet light

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2018.1288 ◽

2018 ◽

Vol 285 (1884) ◽

pp. 20181288 ◽

Cited By ~ 6

Author(s):

David C. Negelspach ◽

Sevag Kaladchibachi ◽

Fabian Fernandez

Keyword(s):

Activity Rhythm ◽

Visible Spectrum ◽

Evolutionary Significance ◽

The Sun ◽

Circadian Pacemaker ◽

Circadian Activity ◽

Ultraviolet A ◽

Similar Time ◽

Uva Light ◽

Uva Radiation

The circadian pacemaker synchronizes to the Earth's rotation by tracking step-by-step changes in illumination that occur as the sun passes the horizon. While twilight progressions of irradiance and colour are considered important stimuli in this process, comparably less thought has been given to the possibility that ultraviolet A (UVA) radiation might actually play a more formative role given its evolutionary significance in shaping 24 h timekeeping. Here, we show that Drosophila activity rhythms can be phase-shifted by UVA light at an energy range seated well below that of the visible spectrum. Because the energy threshold for this resetting matches the incident amount of UVA on the human retina at twilight, our results suggest that UVA light has the potential to function as a similar time cue in people.

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