Effect of substance P on circadian rhythms of firing activity and the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro

The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Although substance P (SP) fibers from retina are found to terminate the SCN, the physiological role of this peptide is uncertain. The 2-deoxyglucose (2-DG) uptake and firing activity in the SCN show a robust circadian change. SP causes an increase in 2-DG uptake by SCN during the subjective night but not during subjective day. SP-induced increase in 2-DG uptake is blocked by co-treatment with the SP receptor antagonist, spantide. Treatment with SP produces phase shifts of circadian rhythm in spontaneous neural activity in SCN neurons with a phase-response curve that is similar to the effect of light pulses to animals under constant darkness. SP-induced phase change is also blocked by pretreatment with spantide. SP-induced increase in 2-DG uptake and phase changes in firing activity occur only during subjective night, at circadian times when photic phase shifting of activity occurs. The present results suggest that SP may be an important transmitter for conveying environmental light-dark information from retina to the SCN.     

Circadian photic regulation of melatonin receptor density in rat suprachiasmatic nuclei: Comparison with light induction of fos-related protein

High-affinity melatonin receptors are present in rat suprachiasmatic nuclei (SCN), and their density exhibits a daily rhythm regulated by the light/dark cycle. In this study we demonstrate that the light regulation of these receptors depends on a circadian mechanism. Pinealectomized rats kept in constant darkness were subjected to 1-hr light pulses delivered across the circadian cycle. The density of melatonin receptors was significantly increased when photic exposure was performed during subjective night, and not different from control animals kept in darkness when the light pulse was applied during subjective day. The protein product (Fos) of the immediate early gene c-fos studied in the same paradigm showed globally the same circadian sensitivity phase. These results clearly show that, although the rhythmic appearance of melatonin receptor density in SCN follows and is directly regulated by the standard light/dark cycle, this light regulation is not passive. As is the case with Fos-like protein, it is only during a precise phase of the circadian cycle that light is able to regulate the density of melatonin receptors in SCN. © 1996 Wiley-Liss,Inc.     

Nerve growth factor-induced circadian phase shifts and MAP kinase activation in the hamster suprachiasmatic nuclei

Circadian rhythms are entrained by light and by several neurochemical stimuli. In hamsters housed in constant darkness, i.c.v. administration of nerve growth factor (NGF) at various times in their circadian cycle produced phase shifts of locomotor activity rhythms that were similar in direction and circadian timing to those produced by brief pulses of light. Moreover, the effect of NGF and light were not additive, indicating signalling points in common. These points include the immediate-early gene c-fos and ERK1/2, a component of the mitogen-activated protein kinases (MAPK) family. NGF activates c-FOS and ERK1/2-MAPK in the suprachiasmatic nuclei, the site of a circadian clock in mammals, when administered during the subjective night but not during the day. The effect of NGF on ERK1/2 activation was not inhibited by the administration of MK-801, a glutamate/NMDA receptor antagonist. These results suggest that NGF, acting through MAPK activation, plays a role in photic entrainment of the mammalian circadian clock.     

Entrainment and coupling of the hamster suprachiasmatic clock by daily dark pulses

The circadian rhythm of locomotor activity of hamsters kept in constant light (LL) can split into two distinct components that, in steady state, lie 180 degrees apart. The splitting phenomenon is the result of antiphase circadian oscillations between left and right sides of the suprachiasmatic nuclei (SCN), the master circadian clock in mammals. In unsplit hamsters housed in LL, a single dark pulse produces a phase-shift of the wheel-running activity rhythm, accompanied by a transient down-regulation of clock gene expression in the SCN. In the present study, we evaluated the effects of daily 1-hr dark pulses on wheel-running activity rhythm and on the expression of clock and nonclock proteins in the SCN of Syrian hamsters exposed to LL conditions. The results show that a daily 1-hr dark pulse entrained the rhythm of wheel-running activity of unsplit hamsters. In addition, in split animals, unimodal coupling of the two locomotor activity components was produced by daily 1-hr dark pulses. In the SCN, the effects of entrainment and unimodal coupling of the two separate components by dark observed in behavior were also evident in the bilateral expression of the proteins c-FOS, p-ERK, PERIOD 1, and calbindin. These results show that the bilaterally asymmetric SCN clock, underlying split circadian behavior, can be recoupled in phase and entrained by short daily dark exposure, indicating the synchronizing potency of darkness on the main circadian clock.     

Circadian clock in cell culture: II. In vitro photic entrainment of melatonin oscillation from dissociated chick pineal cells

The avian pineal gland contains circadian oscillators that regulate the rhythmic synthesis of melatonin. We have developed a flow-through cell culture system in order to begin to study the cellular and molecular basis of this vertebrate circadian oscillator. Pineal cell cultures express a circadian oscillation of melatonin release for at least 5 cycles in constant darkness with a period close to 24 hr. In all circadian systems, light regulates the rhythm by the process of entrainment that involves control of the phase and period of the circadian oscillator. In chick pineal cell cultures we have investigated the entraining effects of light in 2 ways: by shifting the light-dark cycle in vitro and by measuring the phase-shifting effects of single light pulses. A 6 hr advance or delay of a LD 12:12 light-dark cycle produced a corresponding shift in the melatonin rhythm. The phase shifts of the rhythms persisted after transfer to constant darkness, showing that the underlying circadian oscillator was entrained. Photic entrainment of the oscillator was further characterized by measuring the phase-shifting effects of single 6 hr light pulses. Single pulses of light shifted the phase of the circadian oscillator in a phase-dependent manner. Light pulses beginning early in the subjective night delayed the phase of the oscillation 8 hr relative to dark controls. Conversely, light pulses beginning late in the subjective night advanced the phase of the oscillation nearly 8 hr. Thus, photoreceptors within the cell cultures can mediate entrainment of the pineal oscillators.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intergeniculate leaflet lesions on circadian rhythms in Octodon degus

The intergeniculate leaflet (IGL) modulates photic and nonphotic entrainment of circadian rhythms in nocturnal species, but nothing is known about its role in diurnal species. We investigated the significance of the IGL for circadian rhythm function in the diurnal rodent, Octodon degus, by determining the effects of bilateral electrolytic IGL lesions (IGL_X) on: (i) photic entrainment; (ii) reentrainment rates to photic cues following a 6-h phase advance of the light–dark (LD) cycle; (iii) reentrainment rates to nonphotic social and photic cues following a 6-h phase advance of the LD cycle; and (iv) the circadian period (τ) of the activity rhythm in constant darkness (DD). IGL_X significantly lengthened the duration (α) of the entrained activity rhythm and produced a significantly earlier phase of activity onset under entrained (LD 12:12) conditions, but did not change phase of activity offset, rhythm amplitude or mean daily activity levels. IGL_X failed to modify τ of free-running activity rhythms in DD or alter reentrainment rates of circadian rhythms to nonphotic social and photic cues or photic cues alone. Thus, the IGL modulates two parameters of photic entrainment, but is not necessary for reentrainment to either nonphotic social or photic cues. Our results contribute to the growing comparative database on the neural mechanisms controlling circadian rhythms and indicate that the role of the IGL varies across species with no apparent relationship between diurnality–nocturnality and circadian function.     

Morphine-induced activity attenuates phase shifts to light in C57BL/6J mice.

Circadian rhythms can be phase shifted and entrained by daily schedules of light and by non-photic stimuli such as locomotor activity. Relatively little is known of how photic and non-photic stimuli interact to regulate circadian phase. Morphine injections were used to examine the effects of locomotor activity on phase shifts to light pulses in mice free-running in constant dark. Morphine injections scheduled early or late in the active period (subjective night) induced hyperactivity, but did not induce phase shifts. Light pulses late in the subjective night induced phase advance shifts that were significantly attenuated (63% smaller, p<0. 01) by pretreatment with morphine. This inhibitory effect of morphine on light-induced phase advances was blocked by preventing mice from running for 6 h after the injections. Light pulses early in the subjective night induced phase delay shifts that were only weakly attenuated (15% smaller, p=0.06) by morphine. These results demonstrate behavioral inhibition of light-induced phase resetting of circadian rhythms in mice, and suggest that the strength of this effect may be phase dependent, although other interpretations are possible.     

Chronic BMY7378 treatment alters behavioral circadian rhythms

The mammalian circadian clock is synchronized to the day : night cycle by light. Serotonin modulates the circadian effects of light, with agonists inhibiting response to light and antagonists enhancing responses to light. A special class of serotonergic compounds, the mixed 5‐HT_1A agonist/antagonists, potentiates light‐induced phase advances by up to 400% when administered acutely. In this study, we examine the effects of one of these mixed 5‐HT_1A agonist/antagonists, BMY7378, when administered chronically. Thirty adult male hamsters were administered either vehicle or BMY7378 via surgically implanted osmotic mini pumps over a period of 28 days. In a light : dark cycle, chronic BMY7378 advanced the phase angle of entrainment, prolonged the duration of the active phase and attenuated the amplitude of the wheel‐running rhythm during the early night. In constant darkness, chronic treatment with BMY7378 significantly attenuated light‐induced phase advances, but had no significant effect on light‐induced phase delays. Non‐photic phase shifts to daytime administration of a 5‐HT_1A/7 agonist were also attenuated by chronic BMY7378 treatment. qRT‐PCR analysis revealed that chronic BMY7378 treatment upregulated mRNA for 5‐HT_1A and 5‐HT_1B receptors in the hypothalamus and downregulated mRNA for 5‐HT_1A and monoamine oxidase‐A in the brainstem. These results highlight adaptive changes of serotonin receptors in the brain to chronic treatment with BMY7378 and link such up‐ and downregulation to changes in important circadian parameters. Such long‐term changes to the circadian system should be considered when patients are treated chronically with drugs that alter serotonergic function.     

Neonatal exposure to constant light prevents anhedonia-like behavior induced by constant light exposure in adulthood

Depressive episodes are associated with disturbances in circadian rhythms, and constant illumination has been reported to induce depressive-like behavior in rodents. Rats kept in constant darkness express the endogenous circadian rhythm, and most animals under constant light conditions lose circadian locomotor rhythmicity. Exposure to constant light in rats during lactation was reported to prevent this loss of circadian rhythm in adulthood. Thus, the aim of the present study was to verify whether exposure to constant light during lactation prevents anhedonia-like behavior induced by constant light in adult rats. In experiment 1, we replicated the anhedonia-like effects of constant light in adult male rats. We showed that this effect is reversed by imipramine treatment in the drinking water. In experiment 2, we subjected rats to constant darkness (neonatal-DD), constant light (neonatal-LL) or to normal light/dark cycle (neonatal-LD) during the neonatal phase and evaluated them after constant light exposure in adulthood. The group exposed to constant light during the neonatal phase did not reduce their sucrose preference and exhibited greater locomotor activity than the other groups. The neonatal-DD group exhibited decreased sucrose preference earlier than controls and had higher serum corticosterone concentrations. Prevention of arrhythymicity might protect neonatal-LL rats from anhedonia-like behavior induced by constant light, whereas constant darkness during the neonatal phase rendered the neonatal-DD group more susceptible to depressive-like behavior. These results corroborate with the literature data indicating that circadian disruption may contribute in mood disorders and that early life stress can influence stress responsivity in adulthood.     

Investigation Into the Regulation of the Circadian System by Dopamine and Melatonin in the Adult Siberian Hamster (Phodopus sungorus)

Dopamine and melatonin have both been implicated in mediating maternal influences on the developing circadian system of altricial rodents. The aim of these studies was to investigate their role in the entrainment of the circadian system of the adult Siberian hamster (Phodopus sungorus). In-situ hybridization revealed that D₁-dopamine receptor (D₁-R) mRNA was expressed in the adult suprachiasmatic nucleus (SCN) at levels comparable to neonates. As dopamine has been postulated to mimic photic stimulation during early development, experiment 1 compared the effects of a D₁-R agonist and a light pulse on free-running wheel running rhythms in hamsters maintained in constant dim red light. A phase response curve to light was generated, revealing clear phase delays early in the subjective night, and large phase advances in the late subjective night. However, the D₁-R agonist (SKF 81297, 2 mg/kg, s.c.) did not produce consistent phase shifts at any circadian phase. Experiment 2 tested the ability of this dopaminergic agonist to modulate photic responses of the circadian system. Free-running animals were pre-treated with SKF 81297 (2 mg/kg, s.c.) 30 min before a 15 min light pulse given early or late in the subjective night. This agonist had no effect on the magnitude of phase shifts at either circadian time. In experiment 3, light pulses at CT13–15 induced expression of the immediate early gene c-fos in the SCN, as assessed by immunocytochemistry for the protein product. In contrast, SKF 81297 (2 mg/kg, s.c.) at the same phase did not induce c-fos in the SCN, despite marked c-fos induction in the caudate-putamen, nor did it affect photic induction of c-fos in the SCN. To investigate whether dopamine might be involved in nonphotic regulation of the circadian system in adult hamsters, experiment 4 compared the response of free-running hamsters to a series of injections of SKF 81297 (2 mg/kg, s.c.) or melatonin (1 mg/kg, s.c.), since melatonin receptor expression in the SCN also persists into adulthood. Animals were treated every 23.5 h for 6 days. The serial injections of melatonin produced cumulative phase advances of up to 3 h when delivered in late subjective day, but not when presented in late subjective night. Hamsters did not respond to SKF 81297 or vehicle treatment at either circadian phase. Moreover, pre-treatment with the dopaminergic agonist did not affect the phase-advancing effects of melatonin when both were given in the serial injection protocol. These results demonstrate clear phase-dependent effects of light pulses and melatonin on circadian rhythms in Siberian hamsters, but suggest that D₁-Rs in the SCN no longer modulate photic or melatonin-dependent entrainment pathways in the adult.     

Circadian rhythm of melatonin release from the photoreceptive pineal organ of a teleost, ayu (Plecoglossus altivelis) in flow-thorough culture

In the present study, we tested whether the pineal organ of ayu (Plecoglossus altivelis), an osmerid teleost close relative of salmonids, harbours a circadian oscillator regulating rhythmic melatonin release using flow-through culture. The pineal organ maintained under light/dark cycles released melatonin in a rhythmic fashion with high levels during the dark phase. A circadian rhythm of melatonin release persisted in constant darkness for at least four cycles. Characteristics of the circadian rhythm (free-running period, phase and amplitude) exhibited small variations among cultures when the data was normalized, indicating that this system is sufficient for the analysis of the circadian rhythm both at qualitative and quantitative levels. Six-hour extension of the light phase from the normal onset time of the dark phase or exposure to constant light for 36 or 48 h before transfer to constant darkness significantly inhibited melatonin release. Phase shifts in the circadian rhythm of melatonin release were also observed. Thus, the ayu pineal organ contains all the three essential components of the circadian system (a circadian clock, the photoreceptor responsible for photic entrainment of the clock, and melatonin generating system as an output pathway). This system should provide a useful model for analysing the physiological and molecular basis of the vertebrate circadian system. In addition, further comparative studies using salmonids and related species including ayu will provide some insight into the evolution of the roles of the pineal organ in the vertebrate circadian system.     

Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: Anatomical and functional consequences on the circadian system

In rodents, daily injection of neurotoxic monosodium L-glutamate (MSG) during the postnatal period induces retinal lesions, optic nerve degeneration with an alteration of visual pathway and an absence of the b-wave in the electroretinogram. Despite this damage, electrophysiological responses subsist in the lateral geniculate bodies and synchronization of circadian rhythms to the light/dark cycle can still occur. Using two formal properties of the circadian system (entrainment and phase-shift by light), we assessed the functionality of retinal projections to the circadian clock in MSG-treated hamsters. Displaced amacrine and ganglion cell populations were quantified and retinal terminals in the suprachiasmatic nuclei were estimated. Animals received daily doses of glutamate during the first ten days after birth according to two protocols. The two treatments similarly destroyed 56% of the overall population of the ganglion cell layer: 30% of displaced amacrine and 89% of ganglion cells. Surviving ganglion neurons (7,500 cells) were evenly distributed across the entire retina except in one area of high cell density located in the temporoventral quadrant. Retinal projections of the “image-forming” pathway were drastically reduced in the dorsal lateral geniculate bodies, less in their ventral part. The “nonimage-forming” pathway was also affected since the volume of labeled terminals in the suprachiasmatic nuclei was reduced by one-half to one-third. Nevertheless, treated hamsters exhibited a free-running locomotor activity rhythm after several months in constant darkness, could be entrained by the light/dark cycle and phase-shifted by light pulses. These results suggest that a damaged retinohypothalamic tract can still assume the photic entrainment of the circadian clock. 1993 Wiley-Liss, Inc. © 1993 Wiley-Liss, Inc.     

Removal of the olfactory bulbs delays photic reentrainment of circadian activity rhythms and modifies the reproductive axis in male Octodon degus

The diurnal rodent, Octodon degus, exhibits robust sex differences in several circadian measures, including circadian period (τ) and reentrainment rates to photic and nonphotic (social) zeitgebers. The neural substrates underlying such physiological differences remain unknown. In female degus, olfactory bulbectomies (BX) inhibit socially-facilitated reentrainment, but do not alter photic reentrainment, entrained measures, or τ in constant darkness (DD). This experiment investigated the effects of BX in male degus on (i) photic reentrainment rates of circadian rhythms following a 6-h phase advance of the light–dark (LD) cycle; (ii) photic entrainment; (iii) τ of free-running activity rhythms in DD; and (iv) body weight, paired testis weight, and the reproductive hormones, testosterone, androstenedione and follicle stimulating hormone (FSH). BX significantly delayed photic reentrainment rates. They did not, however, modify τ, the phase of activity onset or offset, amplitude or duration (α) of the activity rhythm, mean daily locomotor activity levels, or body weight. FSH, testosterone and androstenedione were unaffected by BX, whereas paired testis weights were significantly greater in BX degus compared with shams. Thus, the olfactory bulbs influence photic reentrainment of circadian rhythms and modestly affect the reproductive axis in male degus. Our results suggest that the olfactory bulbs may be a neural source of observed sex differences in photic reentrainment in degus, and highlight interspecies variation in the olfactory bulbs' effects on entrained and free-running circadian rhythms and on reproduction.     

Functions of corazonin and histamine in light entrainment of the circadian pacemaker in the Madeira cockroach,Rhyparobia maderae

The circadian pacemaker of the Madeira cockroach, Rhyparobia (Leucophaea) maderae, is located in the accessory medulla (AME). Ipsi‐ and contralateral histaminergic compound eyes are required for photic entrainment. Light pulses delay locomotor activity rhythm during the early night and advance it during the late night. Thus, different neuronal pathways might relay either light‐dependent delays or advances to the clock. Injections of neuroactive substances combined with running‐wheel assays suggested that GABA, pigment‐dispersing factor, myoinhibitory peptides (MIPs), and orcokinins (ORCs) were part of both entrainment pathways, whereas allatotropin (AT) only delayed locomotor rhythms at the early night. To characterize photic entrainment further, histamine and corazonin were injected. Histamine injections resulted in light‐like phase delays and advances, indicating that the neurotransmitter of the compound eyes participates in both entrainment pathways. Because injections of corazonin only advanced during the late subjective night, it was hypothesized that corazonin is only part of the advance pathway. Multiple‐label immunocytochemistry in combination with neurobiotin backfills demonstrated that a single cell expressed corazonin in the optic lobes that belonged to the group of medial AME interneurons. It colocalized GABA and MIP but not AT or ORC immunoreactivity. Corazonin‐immunoreactive (‐ir) terminals overlapped with projections of putatively light‐sensitive interneurons from the ipsi‐ and contralateral compound eye. Thus, we hypothesize that the corazonin‐ir medial neuron integrates ipsi‐ and contralateral light information as part of the phase‐advancing light entrainment pathway to the circadian clock. J. Comp. Neurol. 525:1250–1272, 2017. © 2016 Wiley Periodicals, Inc.     

Photic regulation of Fos-like immunoreactivity in the suprachiasmatic nucleus of the mouse.

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus functions as the primary pacemaker of the circadian system. Light has been shown to induce Fos-like immunoreactivity (Fos-LI) in the SCN of rats and hamsters. The purpose of the present study was to evaluate extensively the effect of light on Fos-LI in the mouse SCN. Brief pulses of light administered to animals otherwise in constant darkness were found to induce Fos-LI. This photic induction was unaffected by the rd mutation, which causes the profound loss of photoreceptors but fails to affect circadian responses to light. Light regulation of Fos-LI was dependent upon the phase of the circadian cycle in which the light pulse was administered. Phases at which light causes phase shifts of the circadian system were permissive for Fos-LI induction (CT 16 and 24), while phases in which light does not cause phase shifts were not permissive (CT 6 and 9). The time course of the induction at CT 16 was also described. In a light/dark cycle, Fos-LI was found to be rhythmically expressed with Fos-LI elevated soon after the lights came on but remaining low throughout the rest of the cycle. However, this rhythm is a direct consequence of the light because in constant darkness Fos-LI was always low. These results have implications regarding the possible functional roles of Fos in the circadian system and add to our understanding of light regulation of circadian physiology in the mouse.     

Photic control of nitric oxide synthase activity in the hamster suprachiasmatic nuclei

Circadian rhythms are controlled by an endogenous clock, which in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN). A role for nitric oxide in circadian responses to light has been indicated. To test the role of nitric oxide synthase (NOS) in the SCN and in circadian responses to light, we examined NOS specific activity at different time points and photic conditions. NOS activity was determined by the conversion of -arginine to -citrulline. NOS enzymatic activity in the SCN was significantly higher during the dark phase than during the day, without any changes in the levels of the NOS protein. However, this difference disappeared when animals were placed under constant darkness, and NOS activity was similar at CT 8 and CT 18 (with CT 12 defined as the onset of the subjective night). When 5-min light pulses were administered at these time points (when light would induce no phase shift or a phase advance, respectively), NOS activity was significantly increased almost equally. A spectrophotometric assay was used to determine NO content in the SCN, showing relatively high constitutive levels enhanced by 100 μM glutamate. These results suggest that NOS activity is not controlled by the circadian clock, although it might mediate some of the effects of light on biological rhythms.     

Temperature cycles drive Drosophila circadian oscillation in constant light that otherwise induces behavioural arrhythmicity

The fruit fly, Drosophila melanogaster, shows a clear circadian locomotor rhythm in light cycles and constant darkness. Although the rhythm disappears in constant light, we found that temperature cycles drive the circadian rhythm both in locomotor activity and molecular abundance of PERIOD (PER) and TIMELESS (TIM). The thermoperiodically induced locomotor rhythm entailed an anticipatory activity at the late thermophase, which required several transient cycles to establish a steady-state entrainment, suggesting that the rhythm is endogenous and driven by a circadian clock. Western blot analysis revealed that PER and TIM increased during the cryophase, peaking at the middle to late cryophase. PER was also cyclically expressed under the temperature cycle in the known per-expressing neurons, i.e. so-called lateral (LNs) and dorsal neurons (DNs), and two pairs of cells (LPNs) that were located in the lateral posterior protocerebrum. It is thus suggested that the temperature cycle induces the cycling of PER and TIM either by blocking somewhere in the photic entrainment pathway during the cryophase or temporally activating their translation to sufficient protein levels to drive a circadian oscillation. In flies lacking pigment-dispersing factor (PDF) or PDF-expressing cells, the anticipatory activity was relatively dispersed. disco(2) mutant flies lacking the lateral neurons still showed an anticipatory activity, but with dispersed activity. These behavioural results suggest that not only LNs but also DNs and LPNs can, at least, partially participate in regulating the thermoperiodically induced rhythm.     

Effect of variable temperatures, darkness and light on the secretion of melatonin by pineal explants in the gecko, Christinus marmoratus

This study examined the combined effect of thermocycles with either variable or constant photic conditions on melatonin production by pineal organs in vitro in the gecko. Christinus marmoratus. A 30°C:15°C thermocycle elicited a rhythm of melatonin production under conditions of 12L:12D, constant light or constant darkness when the cryophase coincided with the dark phase of the photocycle or with the subjective night. A 6 h advance of the thermocycle with respect to the photocycle produced an advance in the onset and offset of melatonin production in subsequent nights. When the thermocycle was 180° out of phase with the photoperiod, the rhythm of melatonin production was disrupted, suggesting a differential pattern of sensitivity to photothermal stimuli. It was concluded that both light and temperature are important modulators of pineal function although their combined effects on pineal melatonin production is complex and unclear.     

Shedding light on circadian clock resetting by dark exposure: differential effects between diurnal and nocturnal rodents

The master circadian clock in mammals, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, is entrained by light and behavioural stimulation. In addition, the SCN can be reset by dark pulses in nocturnal rodents under constant light conditions. Here, the shifting effects of a dark pulse on the SCN clock were detailed at both a behavioural and molecular level in a nocturnal rodent (Syrian hamster), and were compared to those of a diurnal rodent (Arvicanthis ansorgei). Four-hour dark pulses led to phase advances in the circadian rhythm of locomotor activity from subjective midday to dusk in hamsters, but from subjective dusk to midnight in Arvicanthis. Moreover, dark pulses had no resetting effect during the middle of the subjective night in hamsters, while such a dead shifting zone occurred during most of the subjective day in Arvicanthis. The behavioural phase advances in both hamsters and Arvicanthis were most often accompanied by marked downregulation of the clock genes Per1 and/or Per2 in the SCN, and also by changes in the transforming growth factor-alpha expression, a neuropeptide that suppresses daytime activity in nocturnal mammals. Despite that both hamsters and Arvicanthis showed dark-induced phase advances at circadian time-12, Per1 gene and its protein PER1 were downregulated in Arvicanthis but not in hamsters. Altogether these results show that dark resetting of the SCN is always associated with downregulation of Per1 and/or Per2 expression, and mostly occurs during resting. Thus, the circadian window of sensitivity to dark differs between nocturnal and diurnal rodents.