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N Mrosovsky

Publications and source records attributed to N Mrosovsky.

At least 37 records · Page 2Linked to original sources
PubMed2001

Behavioral responses to light in mice with dorsal lateral geniculate lesions.

Light has rapid direct effects on behavior and physiology that may be distinguished from its indirect effects that occur via synchronization of the biological clock. In nocturnal animals, light at night acutely suppresses the wheel running activity usually observed at that time of day. This is known as masking because light masks the overt expression of the circadian activity rhythm. In the present study, we compared the effects of light on wheel running in mice with bilateral electrolytic lesions of the dorsal lateral geniculate nucleus (DLG) to those in sham-operated animals. DLG-lesioned animals exhibited greater suppression of wheel running in response to bright light than did the controls, but failed to exhibit the increased activity in response to dim light observed in intact animals. These findings support the view that masking effects of light on behavior comprise two opposing processes, one that increases activity and is mediated by the classical visual system, and another that suppresses activity and is mediated by a non image-forming irradiance detection system.

Animals↗
PubMed2001

A molecular explanation of interactions between photic and non-photic circadian clock-resetting stimuli.

Non-photic clock-resetting events (arousal and locomotor activity) in the subjective day reduced expression of Period genes in the suprachiasmatic nucleus of hamsters. This decrease was attenuated by a 30-min light pulse occurring during the last 0.5 h of 3.5 h of confinement to a novel running wheel. This provides an example at the molecular level of an interaction between different modalities of synchronizing agents.

Journal Article↗
PubMed2001

Further characterization of the phenotype of mCry1/mCry2-deficient mice.

Mice lacking cryptochromes (mCry1/mCry2-/-) were kept in a 16h light, 8h dark, light-dark (16:8 LD) cycle and were given additional pulses of light of different brightness, starting 2h after dark onset and lasting for 1h. The suppression of wheel running during these light pulses (i.e., masking) was compared to that of wild types. No evidence of any decrement in the masking response to light was detected. As well as studying masking, minor bouts of activity occurring in the main light portion of a light-dark cycle were quantified. One possible explanation of such predark activity is that some damped endogenous process is spared in mCry1/mCry2 double-knockout mice.

Animals↗
PubMed2001

Photic and nonphotic circadian phase resetting in a diurnal primate, the common marmoset.

Despite the considerable literature on circadian entrainment, there is little information on this subject in diurnal mammals. Contributing to this lack of understanding is the problem of separating photic from nonphotic (behavioral) phase-resetting events in diurnal species. In the present study, photic phase resetting was obtained in diurnal common marmosets held under constant dim light (DimDim; <0.5 lx) by using a 20-s pulse of bright light to minimize time available for behavioral arousal. This stimulus elicited phase advances at circadian time (CT) 18-22 and phase delays at CT9-12. Daily presentation of these 20-s pulses produced entrainment with a phase angle of approximately 11 h (0 h = activity onset). Nonphotic phase resetting was obtained under DimDim with the use of a 1-h-induced activity pulse, consisting of intermittent cage agitation and water sprinkling, delivered in total darkness to minimize photic effects. This stimulus caused phase delays at CT20-24, and entrainment to a scheduled daily regimen of these pulses occurred with a phase angle of approximately 0 h. These results indicate that photic and nonphotic phase-response curves (PRCs) of marmosets are similar to those of nocturnal rodents and that nonphotic PRCs are keyed to the phase of the suprachiasmatic nucleus pacemaker, not to the phase of the activity-rest cycle.

Animals↗
PubMed2001

Cycle of period gene expression in a diurnal mammal (Spermophilus tridecemlineatus): implications for nonphotic phase shifting.

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 understanding nonphotic phase response curves in diurnal species and thereby for guiding research on nonphotic phase shifting in people.

Animals↗
PubMed2000

Responses to light after retinal degeneration.

Transgenic rodless mice were given 1-h pulses of light of varying brightness at times of the night when they were normally active. The rodless mice showed decreases in locomotor activity during light pulses brighter than 2 lux; these decreases were significantly greater than those in wildtypes (ANOVA, P < 0.01). However, with very dim light, rodless mice showed no changes in activity, whereas wildtype mice actually increased their activity. It is suggested that irradiance detection could be enhanced by absence of image-forming vision. Enhanced inhibition of activity around twilight may be adaptive for mice in some circumstances and so help maintain genes for retinal degeneration in natural populations.

Animals↗
PubMed2000

Preferences of mice, Mus musculus, for different types of running wheel.

Mice are increasingly used in research. In particular, their wheel running is often used as a measure of activity, and as a marker of phase of circadian rhythms. Learning about the preferences of mice for different types of wheel may improve their welfare and suggest ways of increasing activity levels. Mice, Mus musculus, were given a choice between different types of running wheel by putting them in cages equipped with two wheels. Strong preferences were shown for wheels with a plastic mesh flooring, rather than the standard metal rods only. The mesh was even preferred over a solid base, although this effect was not seen in mice that had been given access only to wheels with the solid base immediately prior to the choice test. Small diameter wheels, sometimes sold as mouse wheels, were preferred less than standard-sized wheels with rods. The results suggest that types of running wheel often used in laboratories can be improved by considering the animals' preferences. The types of wheel tested here are easy to maintain and entail little additional cost, while increasing the mouse's interest in running and exercise.

Animals↗
PubMed1999

Rapid down-regulation of mammalian period genes during behavioral resetting of the circadian clock.

The pervasive role of circadian clocks in regulating physiology and behavior is widely recognized. Their adaptive value is their ability to be entrained by environmental cues such that the internal circadian phase is a reliable predictor of solar time. In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasmatic nuclei (SCN). However, although light can advance or delay the clock during circadian night, behavioral events trigger phase advances during the subjective day, when the clock is insensitive to light. The recent identification of Period (Per) genes in mammals, homologues of dperiod, which encodes a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular level. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acutely up-regulated by light. Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/translational feedback loop. Here we describe circadian oscillations of Per1 and Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscillator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at the molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock.

Animals↗
PubMed1999

Thresholds for masking responses to light in three strains of retinally degenerate mice.

Mutant mice with retinal degeneration (rd/rd) were given 1-h pulses of light of varying brightness at times of the night when they would normally be active. The mutant mice showed a significantly greater inhibition of locomotor activity to light (negative masking) than wildtype controls. Lack of impairment, or even enhancement of negative masking suggests that this response may depend on sparing in retinally degenerate mice of the same receptor type that mediates clock resetting, because synchronization of the circadian system is known to be unimpaired in these mutants. With very dim light pulses, mutants did not change their activity, but wildtypes actually became more active (positive masking). Positive and negative masking appear to depend on different sensory and central processes.

Animals↗
PubMed1999

Masking of locomotor activity in hamsters.

The inhibition of locomotion by light (masking) was investigated in Syrian hamsters. When 1-h pulses of light were presented in the early night, activity was strongly suppressed by irradiances of about 1 lx or greater. Ultradian light-dark cycles were used as another way to study masking. Hamsters were unable to entrain to 3.5:3.5-h light-dark cycles, thus permitting the masking and the entraining effects of light to be distinguished. Light had greater suppressive effects on activity in home cages than on activity in novel running wheels. Moreover, in home cages activity remained very low for about 30 min after lights were turned off. Post-pulse suppression of activity was not simply a consequence of reduced running, as shown by experiments in which running was temporarily prevented by locking the wheels. A phase response curve for masking was obtained by placing hamsters in novel wheels for 3-h periods at various times throughout their circadian cycles, and then superimposing a 30-min light pulse. The suppressive effect of light was maximal around the onset of activity, which normally coincides with dusk in hamsters. This may have adaptive value in limiting foraging to the hours of darkness.

Activity Cycles↗
PubMed1999

Masking by light in hamsters with SCN lesions.

Inhibition of wheel running by light (masking) was investigated in Syrian hamsters with suprachiasmatic nucleus or sham lesions. Approximately 90% of the wheel revolutions made by hamsters with complete suprachiasmatic nucleus lesions, as judged by histology and power spectrum analysis of their wheel running, occurred during the dark phases of an ultradian light-dark cycle (3.5 h light, 3.5 h dark). This was demonstrated for two illumination levels (380 lx and 6 lx). Similar results were obtained with sham-operated animals. In further tests, the hamsters with lesions also retained a strong preference for the dark side of a box divided into dark and light sides. These results demonstrate that the suprachiasmatic nucleus is not necessary for masking by light or the preference for a dark over a light compartment. Evidently the direct effects of light can substitute for the endogenous control by the suprachiasmatic nucleus to maintain appropriate behaviour in time and space.

Activity Cycles↗
PubMed1999

Enhanced masking response to light in hamsters with IGL lesions.

Syrian hamsters with intergeniculate leaflet or sham lesions were given tests with a series of light pulses of gradually decreasing intensities. The light pulses were given early in the night, at zeitgeber time 14-15. The amount of wheel running during the pulses was compared to that in the same hour on a night with no light pulses. Hamsters with intergeniculate leaflet lesions showed a significantly greater suppression of their wheel running in response to light than the sham-lesioned animals. The lesioned animals also had larger negative phase angles of entrainment to the 14:10-h light-dark cycle than sham-operated controls. However, phase shifting in response to light pulses at either zeitgeber time 14 or 18 was not significantly altered by the lesions. Preferences for spending more time in a dark than a light area were not abolished by the lesions. It is concluded that the intergeniculate leaflet in the Syrian hamster cannot be of paramount importance for masking of locomotor activity by light but may play a modulating role.

Activity Cycles↗
PubMed1999

Further experiments on the relationship between the period of circadian rhythms and locomotor activity levels in hamsters.

A number of experiments in the past have demonstrated that rats and mice have shorter free-running circadian rhythms when they have access to a running wheel in their cage. Moreover, within groups of rats and hamsters, individuals making most use of their running wheels tend to have shorter circadian rhythms. However, these effects are not always evident. This article analyzes the results of four additional experiments on hamsters, some showing correlations between high activity and fast rhythms, and others not. It is suggested that failure to find this relationship occurs when there is an insufficient range of activity levels within a group. When present, correlations between locomotor activity and periodicity reflect causal links because shorter rhythms can be produced by providing a type of running wheel on which hamsters run more. The effects of possible changes in activity on circadian period should be considered when interpreting experiments on physiological manipulations of the circadian period.

Animals↗
PubMed1999

Nonphotic entrainment in a diurnal mammal, the European ground squirrel (Spermophilus citellus).

Entrainment by nonphotic, activity-inducing stimuli has been investigated in detail in nocturnal rodents, but little is known about nonphotic entrainment in diurnal animals. Comparative studies would offer the opportunity to distinguish between two possibilities. (1) If nonphotic phase shifts depend on the phase of the activity cycle, the phase response curve (PRC) should be about 180 degrees out of phase in nocturnal and diurnal mammals. (2) If nonphotic phase shifts depend on the phase of the pacemaker, the two PRCs should be in phase. We used the diurnal European ground squirrel (Spermophilus citellus) in a nonphotic entrainment experiment to distinguish between the two possibilities. Ten European ground squirrels were kept under dim red light (<1 lux) and 20 +/- 1 degrees C. During the entrainment phase of the experiment, the animals were confined every 23.5 h (T) to a running wheel for 3 h. The circadian rhythms of 6 squirrels entrained, 2 continued to free run, and 2 possibly entrained but displayed arrhythmicity during the experiment. In a second experiment, a photic pulse was used in a similar protocol. Five out of 9 squirrels entrained, 1 did not entrain, and 3 yielded ambiguous results. During stable entrainment, the phase-advancing nonphotic pulses coincided with the end of the subjective day, while phase-advancing light pulses coincided with the start of the subjective day: mean psi(nonphotic) = 11.4 h; mean psi(photic) = 0.9 h (psi defined as the difference between the onset of activity and the start of the pulse). The data for nonphotic entrainment correspond well with those from similar experiments with nocturnal Syrian hamsters where psi(nonphotic) varied from 8.09 to 11.34 h. This indicates that the circadian phase response to a nonphotic activity-inducing stimulus depends on the phase of the pacemaker rather than on the phase of the activity cycle.

Activity Cycles↗
PubMed1999

Masking: history, definitions, and measurement.

Masking and entrainment are two different processes that result in rhythms in physiology and behavior. Considering its functional importance, lamentably little study has been devoted to masking compared to that lavished on entrainment. This paper discusses the origin and definition of terminology (positive and negative masking, paradoxical masking) and methods of quantifying masking. How masking is scored can greatly influence the interpretation of results.

Animals↗
PubMed1998

Expression of Fos in the circadian system following nonphotic stimulation.

Syrian hamsters, Mesocricetus auratus, were confined to novel running wheels for a 3-h period, starting at approximately circadian time (CT) 4.5 (i.e., approaching the middle of their subjective day). It can be reliably predicted from the amount of running in this situation whether or not there will be a subsequent phase-shift. Expression of the immediate early genes c-fos and fosB was examined by immunocytochemistry in the suprachiasmatic nucleus (SCN), the intergeniculate leaflet (IGL) of the thalamus, and the medial pretectal area of hamsters that ran vigorously in the novel wheel and would have phase-shifted. c-Fos was increased, compared to levels in a control group left in their home cages, in the IGL, and the pretectum (PT), but decreased in the SCN. No significant changes in FosB were detected in any region examined. An additional experiment argued against the possibility that the changes in c-Fos could be attributed to a rapid advance of the pacemaker to a different phase in the circadian cycle. Counts of c-Fos-positive cells in the IGL were similar in animals given pulses of running starting at CT 4.5 and starting at CT 12.5-16 (i.e., in the subjective night when they would have been active anyway). Altogether the results support the view that activation of the IGL is important in nonphotic clock resetting, and raise the possibility that the PT may also be involved in nonphotic resetting. However, the results also indicate that novelty-induced running does not alter c-Fos induction in a phase-specific manner in the IGL. The inhibition of c-Fos in the SCN by nonphotic phase-shifting events contrasts with the well-known inducing effects of light pulses. These different effects might underlie some of the interactions between nonphotic and photic zeitgebers when both act together on the circadian system.

Animals↗
PubMed1998

Phase shifting by novelty-induced running: activity dose-response curves at different circadian times.

This study compared phase shifting after novelty-induced running at different circadian times (CTs). In Experiment 1, hamsters were confined to novel wheels for 3 h, starting at CTs 2, 4, 6, 8, 10 or 22. The largest shifts were found at CTs 2, 4 and 6. At each CT there was a relationship between the number of revolutions during the pulse and the size of phase shift. Maximum shifts were usually observed at each CT when animals ran 5000-9000 revolutions during the pulse. In Experiment 2, hamsters were confined to novel wheels for 1 h, also starting at CTs 2, 4, 6, 8, 10 or 22. Unlike with 3-h pulses, the largest shifts with 1-h pulses occurred at CT 8. In Experiment 3, hamsters were shut into a small nest box after a 1-h pulse at CT 8; phase shifting was unaffected, showing that movement about the home cage after a 1-h pulse had ended was not required for shifting. At CTs 2, 4 and 22, 3-h pulses produced shifts but 1-h pulses did not. Possibly, there are two different mechanisms of nonphotic phase shifting that can be activated by being placed in a novel wheel, but the results can also be explained in terms of a single mechanism.

Animals↗