bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing of Testicular Recrudescence in Siberian Hamsters Is Unaffected by Pinealectomy or Long-Day Photoperiod after 9 Weeks in Short Days
Authors: Anchordoquy Hannah C. , Lynch G. Robert
Published: May 2004

In this study, the authors asked whether pinealectomy or temporary exposure to a stimulatory photoperiod affects the timing of spontaneous testicular recrudescence in adult Siberian hamsters chronically exposed to short days (9:15 light:dark). In Experiment 1, hamsters were pinealectomized after 6, 9, or 12 weeks in short days. Pinealectomy after 9 or 12 weeks did not affect the timing of spontaneous gonadal growth (27.7 ± 1.9 and 25.4 ± 1.3 weeks, respectively) compared to sham-operated controls (28.6 ± 0.9 weeks). Enlarged testes occurred earlier in animals that were pinealectomized after 6 weeks in short days (21.8 ± 2.1 weeks). In Experiment 2, adult hamsters were exposed to short days for 9 weeks, transferred to long days (16:8 light:dark) for 4 weeks, and then returned to short days for 23 additional weeks. Although long-day interruption caused gonadal growth in 15 out of 19 hamsters, the temporary long-day exposure did not affect the timing of spontaneous gonadal growth following return to short days (28.2 ± 0.9 weeks) in 10 of the 15, relative to the timing observed in control hamsters continuously maintained in short days (28.2 ± 1.1 weeks). Four out of 19 hamsters did not show gonadal growth following long-day exposure. Spontaneous gonadal growth in these hamsters (28.0 ± 1.4 weeks) also occurred at the same time as controls. The remaining 5 hamsters exhibited enlarged testes following long-day exposure (12.0 ± 0.0 weeks) but were refractory to the second short-day exposure. All hamsters exhibited entrainment of wheel-running activity following the change in photoperiod. Afinal group of 13 animals were pinealectomized before long-day transfer. They exhibited gonadal growth (at 17.2 ± 0.8 weeks) but failed to regress a second time when returned to short days. The timing of gonadal growth in these animals was delayed relative to the sham-operated hamsters temporarily transferred to long days (Experiment 2) but accelerated relative to the hamsters pinealectomized at 9 weeks, which remained continuously in short days (Experiment 1). The results of both experiments suggest that a pineal-independent process mediates the timing of spontaneous gonadal growth in Siberian hamsters chronically exposed to a short-day photoperiod.
mPer1 and mPer2 Are Essential for Normal Resetting of the Circadian Clock
Authors: Albrecht Urs , Zheng Binhai , Larkin David , Sun Zhong Sheng , Lee Cheng Chi
Published: May 2004

Mammalian Per1 and Per2 genes are involved in the mechanism of the circadian clock and are inducible by light. Alight pulse can evoke a change in the onset of wheel-running activity in mice by shifting the onset of activity to earlier times (phase advance) or later times (phase delays) thereby advancing or delaying the clock (clock resetting). To assess the role of mouse Per ( mPer) genes in circadian clock resetting, mice carrying mutant mPer1 or mPer2 genes were tested for responses to a light pulse at ZT 14 and ZT 22, respectively. The authors found that mPer1 mutants did not advance and mPer2 mutants did not delay the clock. They conclude that the mammalian Per genes are not only light-responsive components of the circadian oscillator but also are involved in resetting of the circadian clock.
Assembling a Clock for All Seasons: Are There M and E Oscillators in the Genes?
Authors: Daan S. , Albrecht U. , Van der Horst G. T.J. , Illnerová H. , Roenneberg T. , Wehr T. A. , Schwartz W. J.
Published: May 2004

The hypothesis is advanced that the circadian pacemaker in the mammalian suprachiasmatic nucleus (SCN) is composed at the molecular level of a nonredundant double complex of circadian genes ( per1, cry1, and per2, cry2). Each one of these sets would be sufficient for the maintenance of endogenous rhythmicity and thus constitute an oscillator. Each would have slightly different temporal dynamics and light responses. The per1/ cry1 oscillator is accelerated by light and decelerated by darkness and thereby tracks dawn when day length changes. The per2/ cry2 oscillator is decelerated by light and accelerated by darkness and thereby tracks dusk. These M (morning) and E (evening) oscillators would give rise to the SCN's neuronal activity in an M and an E component. Suppression of behavioral activity by SCN activity in nocturnal mammals would give rise to adaptive tuning of the endogenous behavioral program to day length. The proposition—which is a specification of Pittendrigh and Daan's E-M oscillator model—yields specific nonintuitive predictions amenable to experimental testing in animals with mutations of circadian genes.
Phase Response Curve and Light-Induced Fos Expression in the Suprachiasmatic Nucleus and Adjacent Hypothalamus of Arvicanthis niloticus
Authors: Mahoney Megan , Bult Abel , Smale Laura
Published: May 2004

This article describes the phase response curve (PRC), the effect of light on Fos immunoreactivity (Fos-IR) in the suprachiasmatic nucleus (SCN), and the effect of SCN lesions on circadian rhythms in the murid rodent, Arvicanthis niloticus. In this species, all individuals are diurnal when housed without a running wheel, but running in a wheel induces a nocturnal pattern in some individuals. First, the authors characterized the PRC in animals with either the nocturnal or diurnal pattern. Both groups of animals were less affected by light during the middle of the subjective day than during the night and were phase delayed and phase advanced by pulses in the early and late subjective night, respectively. Second, the authors characterized the Fos response to light at circadian times 5, 14, or 22. Light induced an increase in Fos-IR within the SCN during the subjective night but not subjective day; this effect was especially pronounced in the ventral SCN, where retinal inputs are most concentrated, but was also evident in other regions. Both light and time influenced Fos-IR within the lower subparaventricular area. Third, SCN lesions caused animals to become arrhythmic when housed in a light-dark cycle as well as constant darkness. In summary, Arvicanthis appear to be very similar to nocturnal rodents with respect to their PRC, temporal patterns of light-induced Fos expression in the SCN, and the effects of SCN lesions on activity rhythms.
Patterns of Wheel Running Are Related to Fos Expression in Neuropeptide-Y-Containing Neurons in the Intergeniculate Leaflet of Arvicanthis niloticus
Authors: Smale Laura , McElhinny Teresa , Nixon Joshua , Gubik Betty , Rose Sandra
Published: May 2004

Avariety of nonphotic influences on circadian rhythms have been documented in mammals. In hamsters, one such influence, running in a novel wheel, is mediated in part by the pathway extending from neuropeptide-Y (NPY)-containing cells within the intergeniculate leaflet (IGL) of the thalamus to the hypothalamic suprachiasmatic nucleus (SCN). Arvicanthis niloticus is a species in which all individuals are diurnal with respect to general activity and body temperature when they are housed without a running wheel, but access to a running wheel induces a subset of individuals to become nocturnal. In the first study, the authors evaluated the possibility that nocturnal and diurnal patterns of wheel running in Arvicanthis are correlated with differences in IGL function. Adult male Arvicanthis housed in a 12:12 light-dark (LD) cycle were monitored in wheels, classified as nocturnal or diurnal, and then perfused either 4 h after lights-on or 4 h after lights-off. Sections through the intergeniculate leaflet were processed for immunohistochemical labeling of Fos and NPY. The percentage of NPY cells that expressed Fos was significantly influenced by an interaction between time of day and phenotype such that it rose from night to day in diurnal animals, and from day to night in nocturnal animals. In the second experiment, the authors established that running in a wheel actually induces Fos in the IGLof Arvicanthis. Specifically, the proportion of NPY cells expressing Fos was increased by access to wheels in nocturnal animals at night and in diurnal animals during the day. In the third experiment, the authors established that lesions of the IGL eliminate NPY fibers within the SCN, suggesting that these IGL cells project to the SCN in this species as has been established in other rodents. Together, these data demonstrate a clear difference in NPY cell function in nocturnal and diurnal Arvicanthis that appears to be caused, at least in part, by the differences in their wheel-running patterns, and that NPY cells within the IGL project to the SCN in Arvicanthis.
Seasonality and Photoperiodism in Fungi
Authors: Roenneberg Till , Merrow Martha
Published: May 2004

This review gives a retrospective of what is known about photoperiodism in fungi, which is largely based on reports about seasonal spore concentrations. Relatively few species have been investigated under laboratory conditions, so that our knowledge whether seasonal reproduction in fungi is mainly a direct response to environmental conditions or whether it involves a photoperiodic machinery with memory capacities and a relationship to the circadian system is extremely limited. To form a basis for further experimental endeavors into fungal photoperiodism, we review the reports about endogenous rhythms and photobiology. Finally, we will look at the possibilities of using the fungal circadian model system of Neurospora crassa for future work on photoperiodism.
Decoding Photoperiodic Time and Melatonin in Mammals: What Can We Learn from the Pars Tuberalis?
Authors: Hazlerigg D. G. , Morgan P. J. , Messager S.
Published: May 2004

The cellular and molecular mechanisms through which the melatonin signal is decoded to drive/synchronize photoperiodic responses remain unclear. Much of our current understanding of the processes involved in this readout derives from studies of melatonin action in the pars tuberalis of the anterior pituitary. Here, the authors review current knowledge and highlight critical gaps in our present understanding.
Biology of Mammalian Photoperiodism and the Critical Role of the Pineal Gland and Melatonin
Authors: Malpaux Benoît , Migaud Martine , Tricoire Hélène , Chemineau Philippe
Published: May 2004

In mammals, photoperiodic information is transformed into a melatonin secretory rhythm in the pineal gland (high levels at night, low levels during the day). Melatonin exerts its effects in discrete hypothalamic areas, most likely through MT1 melatonin receptors. Whether melatonin is brought to the hypothalamus from the cerebrospinal fluid or the blood is still unclear. The final action of this indoleamine at the level of the central nervous system is a modulation of GnRH secretion but it does not act directly on GnRH neurones; rather, its action involves a complex neural circuit of interneurones that includes at least dopaminergic, serotoninergic and aminoacidergic neurones. In addition, this network appears to undergo morphological changes between seasons.
Photoperiodism in Humans and Other Primates: Evidence and Implications
Authors: Wehr Thomas A.
Published: May 2004

Most of the anatomical and molecular substrates of the system that encodes changes in photoperiod in the duration of melatonin secretion, and the receptor molecules that read this signal, have been shown to be conserved in monkeys and humans, and the functions of this system appear to be intact from the level of the retina to the level of the melatonin-duration signal of change of season. While photoperiodic seasonal breeding has been shown to occur in monkeys, it remains unclear whether photoperiod and mediation of photoperiod's effects by melatonin influence human reproduction. Epidemiological evidence suggests that inhibition of fertility by heat in men in summer contributes to seasonal variation in human reproduction at lower latitudes and that stimulation of fertility by lengthening of the photoperiod in spring contributes to the variation at higher latitudes. Parallels between the seasonality of human reproduction and seasonal affective disorder suggest that they may be governed by common biological processes. Historical and experimental evidence indicates that human responses to seasonal changes in the natural photoperiod may have been more robust prior to the Industrial Revolution and that subsequently they have been increasingly suppressed by alterations of the physical environment.
Regulation of Seasonal Reproduction in Mollusks
Authors: Wayne Nancy L.
Published: May 2004

Understanding the physiological basis of environmental regulation of reproduction at the cellular level has been difficult or unfeasible in vertebrate species because of the highly complex and diffuse nature of vertebrate neuroendocrine systems. This is not the case with the simple nervous system of mollusks in which reproductive neuroendocrine cells are often readily identifiable in living tissue. Given that there are mollusks that are seasonal breeders, that the neuroendocrine cells controlling reproduction have been identified in several molluskan species, that these neurons are conducive to cell physiological analysis, and that basic features of cell biology have been highly conserved between mammals and mollusks, it seems that the mollusk would provide an excellent model system to investigate cell-physiological events that mediate effects of environmental signals on reproduction. The purpose of this review is to explore this idea in three species in which the topic of the neural basis of seasonal reproduction has been studied: the giant garden slug Limax maximus, the freshwater pond snail Lymnaea stagnalis, and the marine snail Aplysia californica.
Tertian and Quartan Fevers: Temporal Regulation in Malarial Infection
Authors: Garcia Célia R. S. , Markus Regina P. , Madeira Luciana
Published: May 2004

The periodicity in the development of Plasmodium parasites in infected animals, including man, has been known for almost 100 years. In turn, this periodicity is a consequence of the synchronous maturation of the parasite during its intracellular development. The cyclic fever that characterizes malarial infections is the outward manifestation of the parasite development. Until recently, little was known about the mechanisms by which parasite synchronicity is established and maintained. This review surveys the recent literature bearing on two main questions. (1) What are the mechanisms involved in the process of parasite synchronicity? (2) Do the circadian rhythms of the host interfere with the parasite cycle?
Light-Dependent Induction of cFos during Subjective Day and Night in PACAP-Containing Ganglion Cells of the Retinohypothalamic Tract
Authors: Hannibal Jens , Vrang Niels , Card J. Patrick , Fahrenkrug Jan
Published: May 2004

Environmental light stimulation via the retinohypothalamic tract (RHT) is necessary for stable entrainment of circadian rhythms generated in the suprachiasmatic nucleus (SCN). In the current report, the authors characterized the functional activity and phenotype of retinal ganglion cells that give rise to the RHT of the rat. Retinal ganglion cells that give rise to the RHT were identified by transsynaptic passage of an attenuated alpha herpesvirus known to have selective affinity for this pathway. Dual labeling immunocytochemistry demonstrated co-localization of viral antigen and pituitary adenylate cyclase activating polypeptide (PACAP) in retinal ganglion cells. This was confirmed using the anterograde tracer cholera toxin subunit B (ChB). In normal and retinally degenerated monosodium glutamate (MSG)–treated rats, ChB co-localized with PACAP in axons of the retinorecipient zone of the SCN. Light-induced Fos-immunoreactivity (Fos-IR) was apparent in all PACAP-containing retinal ganglion cells and a population of non-PACAP-containing retinal ganglion cells at dawn of normal and MSG-treated animals. Within the next 3 h, Fos disappeared in all non-PACAP-immunoreactive cells but persisted in all PACAP- containing retinal ganglion cells until dusk. When animals were exposed to constant light, Fos-IR was sustained only in the PACAP-immunoreactive (PACAP-IR) retinal ganglion cells. Darkness eliminated Fos-IR in all PACAP-IR retinal ganglion cells, demonstrating that the induction of Fos gene expression was light dependent. When animals were maintained in constant darkness and exposed to light pulses at ZT 14, ZT 19, or ZT 6, Fos-IR was induced in PACAP-IR retinal ganglion cells in a pattern similar to that seen at dawn. Collectively, these data indicate that PACAPis present in ganglion cells that give rise to the RHT and suggest a role for this peptide in the light entrainment of the clock
Cycle of period Gene Expression in a Diurnal Mammal (Spermophilus tridecemlineatus): Implications for Nonphotic Phase Shifting
Authors: Mrosovsky N. , Edelstein K. , Hastings M. H. , Maywood E. S.
Published: May 2004

Ground squirrels, Spermophilus tridecemlineatus, were kept in a 12:12 h light-dark cycle. As expected for a diurnal species, their locomotor activity occurred almost entirely in the daytime. Expression of mPer1 and mPer2 in the suprachiasmatic nucleus was studied at six time points by in situ hybridization. For both these genes, mRNA was highest in the first part of the subjective day (about zeitgeber time 5). This is close to the time when mPer1 and mPer2 expression is maximal in nocturnal rodents. These results have implications for under- standing nonphotic phase response curves in diurnal species and thereby for guiding research on nonphotic phase shifting in people
Profile of 24-h Light Exposure and Circadian Phase of Melatonin Secretion in Night Workers
Authors: Dumont Marie , Benhaberou-Brun Dalila , Paquet Jean
Published: May 2004

Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay (“delayed participants”) and 3 participants showed a circadian adaptation by phase advance (“advanced participants”). The other 22 participants had a timing of melatonin secretion typical of day-oriented people (“nonshifters”). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.
Clockless Yeast and the Gears of the Clock: How Do They Mesh?
Authors: Baler Ruben
Published: May 2004

In spite of its apparent weakness as a clock model, the budding yeast has spawned a technique that has revolutionized our ability to study specific protein-protein interactions like those at the core of the molecular timekeeping mechanisms. Here, the author will summarize the evolution, power, and limitations of this technique and highlight its potential and actual contributions to the field of chronobiology.
Resetting of the Circadian Clock by Phytochromes and Cryptochromes in Arabidopsis
Authors: Yanovsky Marcelo J. , Mazzella M. Agustina , Whitelam Garry C. , Casal Jorge J.
Published: May 2004

The authors sought to investigate the role of phytochromes A and B (phyAand phyB) and cryptochromes 1 and 2 (cry1 and cry2) in the synchronization of the leaf position rhythm in Arabidopsis thaliana. The seedlings were transferred from white light–dark cycles to free-running conditions with or without exposure to a light treatment during the final hours of the last dark period. The phase advance caused by a far-red light treatment was absent in the phyA mutant, deficient in the fhy1 and fhy3 mutants involved in phyAsignaling, and normal in the cry1 and cry1 cry2 mutants. The phase shift caused by blue light was normal in the cry2 mutant; reduced in the phyA, cry1, phyA cry1, and cry1 cry2 mutants; and abolished in the phyA cry1 cry2 triple mutant. The phase shift caused by red light was partially retained by the phyA phyB double mutant. The authors conclude that cry1 and cry2 participate as photoreceptors in the blue light input to the clock but are not required for the phyA-mediated effects on the phase of the circadian rhythm of leaf position. The signaling proteins FHY1 and FHY3 are shared by phyA-mediated photomorphogenesis and phyA input to the clock.
Daily Novel Wheel Running Reorganizes and Splits Hamster Circadian Activity Rhythms
Authors: Gorman Michael R. , Lee Theresa M.
Published: May 2004

The phenomenon of splitting of locomotor activity rhythms in constant light has implied that the mammalian circadian pacemaker is composed of multiple interacting circadian oscillators. Exposure of male Syrian hamsters to novel running wheels also induces splitting in some reports, although novel wheel running (NWR) is better known for its effects on altering circadian phase and the length of the free-running period. In three experiments, the authors confirm and extend earlier reports of split rhythms induced by NWR. Male Syrian hamsters, entrained to LD 14:10, were transferred for 6 to 11 consecutive days to darkened novel Wahmann wheels at ZT 4 and were returned to their home cages at ZT 9. All hamsters ran robustly in the novel wheels. NWR caused a marked reorganization of home cage wheel-running behavior: Activity onsets delayed progressively with each additional day of NWR. After 11 days, activity onset in the nighttime scotophase was delayed by 7 h and disappeared completely in 2 hamsters (Experiment 1). After 6 to 7 days of NWR (Experiment 2), activity onset delayed by 5 h. Transfer of hamsters to constant darkness (DD) after 7 days of NWR revealed clearly split activity rhythms: The delayed nighttime activity bout was clearly identifiable and characterized by a short duration. A second bout associated with the former time of NWR was equally distinct and exhibited a similarly short duration. These components rejoined after 3 to 5 days in DD accomplished via delays and advances of the nighttime and afternoon components, respectively. The final experiment established that rejoining of activity components could be prevented by perpetuating the light-dark:light-dark cycle used to induce split rhythms. The data suggest that NWR causes selective phase shifting of some circadian oscillators and that component oscillators interact strongly in constant darkness.
Molecular Cloning and Circadian Regulation of Cryptochrome Genes in Japanese Quail (Coturnix coturnix japonica)
Authors: Fu Zhengwei , Inaba Misako , Noguchi Tadashi , Kato Hisanori
Published: May 2004

The circadian system is thought to have three components: input, pacemaker (internal clock), and output. Cryptochromes ( Cry) are important clock genes, and recent findings indicate that these genes not only act as circadian photoreceptors but are also essential components in the negative feedback of the circadian system. As a first step toward understanding the avian circadian system, the authors tried to clone Japanese quail homologs of mammalian Crys and analyze their expression patterns in different circumstances. Partial cDNAs of qCry1 and qCry2, which are homologs of mammalian Cry1 and Cry2, respectively, were obtained and their gene expressions were analyzed. Both qCry1 and qCry2mRNAs were present in all the tissues examined. The oscillation patterns of the qCry1 transcripts were tissue specific and generally showed robust changes between daytime and nighttime; except for lung and testis tissues (which showed no detectable changes between daytime and nighttime), daytime levels were higher in all of the tissues examined. This rapid oscillation in qCry1 persisted through constant darkness or constant illumination, indicating that an endogenous clock controls these changes. In contrast, the expression of qCry2 did not oscillate in any tissue examined. In addition, in tissues of the pineal gland and eye, unexpected light exposure in the dark period was able to block the decrease in qCry1 transcripts or induce its expression. These findings, in conjunction with the established roles of CRYs in other species, led the authors to propose that in the circadian system, qCRYs may play important roles similar to the known roles of CRYs of other species, such as acting as circadian photoreceptors and as components of the circadian system.
Neuropeptide Y Differentially Suppresses per1 and per2 mRNA Induced by Light in the Suprachiasmatic Nuclei of the Golden Hamster
Authors: Brewer Judy McKinley , Yannielli Paola C. , Harrington Mary E.
Published: May 2004

Neuropeptide Y (NPY), present in an input pathway to the suprachiasmatic nuclei (SCN), can block the effects of light on circadian rhythms. The authors have studied this interaction using an in vitro brain slice technique. Effects of NPY on light-induced period1 and period2 mRNA in the SCN were examined in vitro following a light pulse during early subjective night. Golden hamsters ( n = 91) were housed under a 14:10 LD cycle and then moved to constant dim red light for 3 days. Hamsters were exposed to a 5-min light pulse previously shown to induce phase shifts and prepared for in vitro application of NPY. Hypothalamic slices containing the SCN were maintained in vitro for 40 min to 4 h after the light pulse, then quick-frozen. Sections were evaluated by in situ hybridization with [35S]-labeled cRNA probes for per mRNA. Rapid light induction of both per1 and per2 by 40 min and 1 h after the light pulse, respectively, was apparent, with NPY inhibition of this response significant by at least these same time points. However, although striking suppression of per2 mRNA by the NPY continued through the peak for per2 at2h, per1 mRNA levels rebounded quickly to equal the per1 induction peak at 1 h and mirrored the control light induction pattern for per1 thereafter. Delaying NPY to 30 min after slice preparation demonstrated that NPY is capable of suppressing peak per1 levels. These results confirm the feasibility of measuring light-induced gene expression in the SCN in vitro. A differential regulation of per1 and per2 transcription might be of critical importance for the modulation of circadian responses to light.
The Suprachiasmatic Nucleus Exhibits Diurnal Variations in Spontaneous Excitatory Postsynaptic Activity
Authors: Lundkvist Gabriella B. , Kristensson Krister , Hill Russell H.
Published: May 2004

A most prominent feature of neurons in the suprachiasmatic nucleus (SCN) is the circadian rhythm in spontaneous firing frequency. To disclose synaptic mechanisms associated with the rhythmic activity, the spontaneous postsynaptic activity was studied using whole-cell, patch clamp recordings in the ventral region of the SCN in slice preparations from rats. The synaptic events were compared between two time intervals corresponding to the highest and lowest electrical activity within the SCN during subjective daytime and nighttime, respectively. The [.gamma]-aminobutyric acid (GABA)–mediated spontaneous inhibitory activity showed no diurnal variations, but the excitatory activity was markedly higher in frequency, without differences in amplitude, during the subjective day compared to the subjective night. Spontaneous and evoked inhibitory synaptic events were blocked by the GABAA receptor antagonist bicuculline. The [.alpha]-amino-hydroxy-5-methylisoxazole-4-propionic acid (AMPA/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked most of the excitatory activity. In addition, CNQX reduced the spontaneous inhibitory activity. The N-methyl-D-aspartate antagonist D-2-amino-5-phosphonopentanoic acid reduced the inhibitory activity to a lesser degree, and there was no significant difference in amplitude or frequency of synaptic events in control and Mg2+-free solutions, indicating that the AMPA receptor plays an important role in regulating the inhibitory release of GABAwithin the SCN. Ipsiand contralateral stimulation of the SCN consistently evoked excitatory synaptic responses. Inhibitory synaptic responses occurred in some neurons upon increasing stimulus strength. In conclusion, this study shows that there is a substantial influence from spontaneous glutamatergic synapses on the ventral part of the SCN and that these exhibit daily variations in activity. Diurnal fluctuations in spontaneous excitatory postsynaptic activity within this network may contribute to the mechanisms for synchronization of rhythms between individual SCN neurons and may underlie the daily variations in the spontaneous firing frequency of SCN neurons.
Tales from the Crypt(ochromes)
Authors: Van Gelder Russell N.
Published: May 2004

Cryptochromes are a family of flavoproteins found in organisms ranging from Arabidopsis to man. Across phylogeny, these proteins have been used for pleiotropic functions ranging from blue-light-dependent development in plants and blue-light-mediated phase shifting of the circadian clock in insects to a core circadian clock component in mammals. Review of the roles of cryptochromes in model organisms reveals several common themes: Multiple cryptochrome family members within individual organisms have redundant functions; cryptochromes used in photic entrainment pathways of the circadian clock are partially redundant with other photopigments; and cryptochromes may function in circadian phototransduction and core clock mechanisms in the same organism, with different functions in different tissues. The present review summarizes recent research on the functions of cryptochrome in the circadian timekeeping and photic entrainment pathways.
Photoperiod-Dependent Response to Androgen in the Medial Amygdala of the Siberian Hamster, Phodopus sungorus
Authors: Cooke Bradley M. , Hegstrom Carol D. , Breedlove S. Marc
Published: May 2004

The medial nucleus of the amygdala (MeA) is a steroid-sensitive region that has been implicated in the expression of behaviors such as mating and aggression. The male Siberian hamster ( Phodopus sungorus) uses light cues to regulate its reproductive neuroendocrine system, reducing androgen synthesis in the autumn and increasing it in the spring. There is also evidence that short photoperiods reduce the sensitivity of the brain to the behavioral effects of androgen. The authors tested the hypothesis that MeA neurons are less responsive to androgen in short photoperiods by comparing the regional volume and average soma size of the four MeA subnuclei (anterodorsal [MeAD], anteroventral [MeAV], posterodorsal [MePD], and posteroventral) in adult male hamsters that had been castrated and then implanted with capsules containing either testosterone (T) or nothing. Animals from each group were housed in either long or short photoperiods for 15 weeks. MeAD and MeAV somata displayed photoperiod-dependent responses to androgen, increasing in size after T treatment only in long days. In contrast, the average soma size and the regional volume of the MePD subnucleus were significantly larger in T-treated males regardless of photoperiod. The authors conclude that photoperiod influences the sensitivity of the MeA to androgen.
Extraocular Light Exposure Does Not Phase Shift Saliva Melatonin Rhythms in Sleeping Subjects
Authors: Lushington K. , Galka R. , Sassi L. N. , Kennaway D. J. , Dawson D.
Published: May 2004

Preliminary work in humans suggests that extraocular light can shift circadian phase. If confirmed, extraocular light may be of therapeutic benefit in the treatment of circadian-related sleep disorders with the advantage over ocular exposure that it can be administered while subjects are asleep. In sleeping subjects, however, the effect of extraocular light exposure on circadian phase has yet to be fully tested. Likewise, there is limited data on the acute effects of extraocular light on sleep and body temperature that may influence its clinical utility. Thirteen subjects [3F, 10M; mean (SD) age = 22.1 (3.0)y] participated in a protocol that totaled 7 nights in the laboratory consisting of a screening phase measurement night followed 1 week later by two counterbalanced experimental sessions each of 3 consecutive nights (habituation, treatment, and posttreatment phase measurement night) separated by 4 days. Saliva was collected for melatonin measurement every half hour from 1800 to 0300 h on the screening night and both the posttreatment phase measurement nights. On the treatment nights, continuous measures of rectal temperature and polysomnographic sleep were collected and overnight urine for measurement of total nocturnal urinary 6-sulphatoxymelatonin excretion. To test for the phase-delaying effects of extraocular light, subjects received either placebo or extraocular light (11,000 lux) behind the right knee from 0100 to 0400 h. Treatment had no significant effect on the onset of saliva melatonin secretion, phase of nocturnal core body temperature, or urinary 6-sulfatoxymelatonin excretion, but a small increase was observed in wakefulness over the light administration period. In summary, extraocular light was not shown to delay circadian phase but was shown to increase wakefulness. The authors suggest that the present protocol has limited application as a treatment for circadian-related sleep disorders.
Entraining Signals Initiate Behavioral Circadian Rhythmicity in Larval Zebrafish
Authors: Hurd Mark W. , Cahill Gregory M.
Published: May 2004

The authors show that a circadian clock that regulates locomotor activity in larval zebrafish develops gradually over the first 4 days of life and that exposure to entraining signals late in embryonic development is necessary for initiation of robust behavioral rhythmicity. When zebrafish larvae were transferred from a light-dark (LD) cycle to constant darkness (DD) on the third or fourth day postfertilization, the locomotor activity of almost all fish was rhythmic on days 5 to 9 postfertilization, with peak activity occurring during the subjective day. Rhythm amplitude was higher after four LD cycles than after three LD cycles. When embryos were transferred from LD to DD on the second day postfertilization, only about half of the animals later displayed statistically significant activity rhythms. These rhythms were noisier and of lower amplitude, but phased normally. When zebrafish were raised in DD beginning at 14 h postfertilization, only 22% of them expressed significant circadian rhythmicity as larvae. These rhythms were of low amplitude and phase-locked to the time of handling on the third day rather than to the maternal LD cycle. These results show that behavioral rhythmicity in zebrafish is regulated by a pacemaking system that is sensitive to light by the second day of embryogenesis but continues to develop into the fourth day. This pacemaking system requires environmental signals to initiate or synchronize circadian rhythmicity.
Behavioral and Neurochemical Investigation of Circadian Time-Place Learning in the Rat
Authors: Aragona Brandon J. , Curtis J. Thomas , Davidson Alec J. , Wang Zuoxin , Stephan Friedrich K.
Published: May 2004

The ability to form an association between the time and the place of food availability, namely time-place learning, is presumably important for survival. The present study was designed toexamine time-place learning and to identify exogenous and endogenous factors that may affect this behavior in rats. In an initial experiment, rats displayed poor time-place behavior and appeared to prefer the feeder that was closer to the center aisle and water supply. When these cueswere minimized in a subsequent experiment, rats consistently displayed the time-place discrimination by exhibiting food anticipatory activity (FAA) at the correct location prior to each mealtime. These rats also showed significant correlations between the level of FAA and the amount of dopamine turnover (the dihydroxyphenylacetic acid/dopamine ratio) in the nucleus accumbens and paraventricular nucleus of the hypothalamus, indicating possible involvement of regional dopaminergic activity in time-place behavior. No correlation was found for norepinephrine, epinephrine, or serotonin. In addition, the correlation between FAA and dopamine turnover was not foundwhen rats were entrained to only one meal per day. Together, the data suggest that rats can learn the time- place discrimination under proper experimental conditions and that dopamine may play a role in the expression of this behavior.
Twilights Widen the Range of Photic Entrainment in Hamsters
Authors: Boulos Ziad , Macchi M. Mila , Terman Michael
Published: May 2004

The range of entrainment of the circadian rhythm of locomotor activity was compared in four groups of Syrian hamsters (eight animals per group) initially exposed to daily light-dark (LD) cycles with either abrupt transitions between light and darkness (LD-rectangular) or simulated twilights (LD- twilight). Lighting was provided by arrays of white light-emitting diodes; daytime illuminance (10 lux) and the total amount of light emitted per day were the same in the two conditions. The period (T) of the LD cycles was then gradually increased to 26.5 h or gradually decreased to 21.5 h, at the rate of 5 min/day. Under LD-rectangular, the upper and lower limits of entrainment were 25.0 to 25.5 h and 22.0 to 22.5 h, respectively, whereas under LD-twilight, 50% of the animals exposed to the lengthening cycles were still entrained at T = 26.5 h and 50% of those exposed to the shortening cycles were still entrained at T = 21.5 h. In a second experiment, two groups of hamsters were exposed to fixedT=25hLD- rectangular ( n = 15) or LD-twilight cycles ( n = 7). Only 33% of the animals entrained in LD-rectangular, whereas 86% of the animals entrained in LD- twilight. Free-running periods in constant darkness were longer following successful entrainment toT=25hbutdidnotdiffer between the animals that entrained to LD-rectangular and those that entrained to LD-twilight. The widening of the range of entrainment observed in LD-twilight indicates that twilight transitions increase the strength of the LD zeitgeber. In LD-twilight, successful entrainment to T = 26.5 h was accompanied by an expansion of activity time to 16.52 ± 1.22 h, with activity onsets preceding mid-dusk by 12.56 ± 2.15 h. Together with earlier data showing similar phase response curves for hour-long dawn, dusk, and rectangular light pulses, these results suggest that the effect of twilights on the range of entrainment may involve parametric rather than nonpara- metric mechanisms.
Different Effects of Intensity and Duration of Locomotor Activity on Circadian Period
Authors: Koteja Pawel , Swallow John G. , Carter Patrick A. , Garland Theodore
Published: May 2004

An outstanding unresolved issue in chronobiology is how the level of locomotor activity influences length of the free-running, endogenous circadian period (•). To address this issue, the authors studied a novel model, 4 replicate lines of laboratory house mice ( Mus domesticus) that had been selectively bred for high wheel-running activity (S) and their 4 unselected control (C) lines. Previous work indicates that S mice run approximately twice as many revolutions/day and exhibit an altered dopaminergic function as compared with C mice. The authors report that S mice have a • shorter by about 0.5 h as compared with C mice. The difference in • was significant both under constant light (control lines: • = 25.5 h; selected: • = 24.9 h) and under constant dark (control lines: 23.7 h; selected: 23.4 h). Moreover, the difference remained statistically significant even when the effects of running speed and time spent running were controlled in ANCOVA. Thus, something more fundamental than just intensity or duration of wheel-running activity per se must underlie the difference in • between the S and C lines. However, despite significant difference in total wheel-running activity between females and males, • did not differ between the sexes. Similarly, among individuals within lines, • was not correlated with wheel-running activity measured as total revolutions per day. Instead, • tended to decrease with average running speed but increase with time spent running. Finally, within individuals, an increase in time spent running resulted in decreased • in the next few days, but changes in running speed had no statistically significant effect. The distinctions between effects of duration versus intensity of an activity, aswell as between the among- versus within-individual correlations, are critical to understanding the relation between locomotor activity and pace of the circadian clock.
The Suprachiasmatic Nucleus: A Clock of Multiple Components
Authors: Lee Han S. , Billings Heather J. , Lehman Michael N.
Published: May 2004

Although impressive progress has been made in understanding the molecular basis of pacemaker function in the suprachiasmatic nucleus (SCN), fundamental questions about cellular and regional heterogeneity within the SCN, andhowthis heterogeneity might contribute toSCNpacemaker function at a tissue level, have remained unresolved. To reexamine cellular and regional heterogeneity within the SCN, the authors have focused on two key questions: which SCN cells are endogenously rhythmic and/or directly light responsive? Observations of endogenous rhythms of electrical activity, gene/protein expression, and protein phosphorylation suggest that the SCN in mammals examined to dateis composed of anatomically distinct rhythmic and nonrhythmic components. Endogenously rhythmic neurons are primarily found in rostral, dorsomedial, and ventromedial portions of the nucleus; at mid and caudal levels, the distribution of endogenously rhythmic cells in the SCN has the appearance of a “shell.” The majority of nonrhythmic cells, by contrast, are located in a central “core” region of the SCN, which is complementary to the shell. The location of light-responsive cells, defined by direct retinohypothalamic input and light-induced gene expression, largely overlaps the location of nonrhythmic cells in the SCN core, although, in hamsters and mice light-responsive cells are also present in the ventral portion of the rhythmic shell. While the relative positions of rhythmic and light-responsive components of the SCN are similar between species, the precise boundaries of these components, and neurochemical phenotype of cells within them, are variable. Intercellular communication between these components may bea key featurer esponsiblefor theuniquepace maker properties of the SCN observed at a tissue and whole animal level.
New Quantitative Trait Loci for the Genetic Variance in Circadian Period of Locomotor Activity between Inbred Strains of Mice
Authors: Hofstetter J. R. , Trofatter J. A. , Nurnberger J. I. , Kernek K. L. , Mayeda A. R.
Published: May 2004

Provisional quantitativetrait loci (QTL) for circadian locomotor period and wheel-running period have been identified in recombinant inbred (RI) mouse strains. To confirm thoseQTLand identify newones, the geneticcomponent of variance of the circadian period was partitionedamongan F2 intercross of RI mouse strains (BXD19 and CXB07). First, a genomic survey using 108 SSLP markers with an average spacing of 15 cM was carried out in a population of 259 (BXD19 · CXB07)F2 animals. The genome-wide survey identified two significant QTLfor period of locomotor activity measured by infrared photobeam crossings on mousechromosomes 1 (lod score5.66) and 14 (lod score4.33). TheQTL on distal chromosome 1 confirmed a previous report based on congenic B6.D2-Mtv7a/ Ty mice. Lod scores greater than 2.0 were found on chromosomes 1, 2, 6, 12, 13, and 14. In a targeted extension study, additional genotyping was performed on these chromosomes in the full sample of 341 F2 progeny. The 6 chromosome-wide surveys identified 3 additional QTL on mouse chromosomes 6, 12, and 13. The QTLon chromosome 12 overlaps with circadian period QTLidentified in several prior studies. For wheel-running period, the chromosome-wide surveys identified QTLon chromosomes 2 and 13 and one highly suggestive QTLon proximal chromosome 1. The results are compared to other published studies of QTL of circadian period.
Validation of Horne and Ostberg Morningness-Eveningness Questionnaire in a Middle-Aged Population of French Workers
Authors: Taillard Jacques , Philip Pierre , Chastang Jean-François , Bioulac Bernard
Published: May 2004

As suggested by the authors, the Horne and Ostberg morning/evening questionnaire (MEQ) has never been adapted to evaluate a nonstudent population. The purpose of this study was to validate this MEQ in a sample of middle-aged workers by modifying only the cutoffs. It was administered in 566 non-shift-workers aged 51.2 to 3.2 years who presented no sleep disorders. According to the Horne and Ostberg classification, the sample consisted of 62.1% morning type, 36.6% neither type, and 2.2% evening type. Multiple correspondence analysis, which determines the principal components, was performed on all MEQ items. Then an ascending hierarchical classification was applied to determine 3 clusters from these principal components. On the basis of these 3 clusters, new cutoffs were determined: evening types were considered as scoring under 53 and morning types above 64, thus giving 28.1% morning type, 51.7% neither type, and 20.2% evening type. As an external validation, eveningness was associated with later bedtime and waking-up time (more pronounced at the weekend), greater need for sleep, larger daily sleep debt, greater morning sleepiness, and ease of returning to sleep in the early morning. A positive correlation between age and morningness was again found. This study confirms that “owls” are not rare in a middle-aged sample. We conclude that this adapted MEQ could be useful when investigating age-related changes in sleep.
Circadian Synchronization and Rhythmicity in Larval Photoperception-Defective Mutants of Drosophila
Authors: Malpel Sébastien , Klarsfeld André , Rouyer François
Published: May 2004

A single light episode during the first larval stage can set the phase of adult Drosophila activity rhythms, showing that a light-sensitive circadian clock is functional in larvae and is capable of keeping time throughout development. These behavioral data are supported by the finding that neurons expressing clock proteins already exist in the larval brain and appear to be connected to the larval visual system. To define the photoreceptive pathways of the larval clock, the authors investigated circadian synchronization during larval stages in various visual systems and/or cryptochrome-defective strains. They show that adult activity rhythms cannot be entrained by light applied to larvae lacking both cryptochrome and the visual system, although such rhythms were entrained by larval stage-restricted temperature cycles. Larvae lacking either pathway alone were light entrainable, but the phase of the resulting adult rhythm was advanced relative to wild-type flies. Unexpectedly, adult behavioral rhythms of the glass60 j and norpA P24 visual system mutants that were entrained in the same conditions were found to be severely impaired, in contrast to those of the wild type. Extension of the entrainment until the adult stage restored close to wild-type behavioral rhythms in the mutants. The results show that both cryptochrome and the larval visual system participate to circadian photoreception in larvae and that mutations affecting the visual system can impair behavioral rhythmicity.