Biomedical subjects

M R Gorman

Publications and source records attributed to M R Gorman.

At least 19 recordsLinked to original sources

PubMed2004

Dim nocturnal illumination alters coupling of circadian pacemakers in Siberian hamsters, Phodopus sungorus.

The circadian pacemaker of mammals comprises multiple oscillators that may adopt different phase relationships to determine properties of the coupled system. The effect of nocturnal illumination comparable to dim moonlight was assessed in male Siberian hamsters exposed to two re-entrainment paradigms believed to require changes in the phase relationship of underlying component oscillators. In experiment 1, hamsters were exposed to a 24-h light-dark-light-dark cycle previously shown to split circadian rhythms into two components such that activity is divided between the two daily dark periods. Hamsters exposed to dim illumination (<0.020 lx) during each scotophase were more likely to exhibit split rhythms compared to hamsters exposed to completely dark scotophases. In experiment 2, hamsters were transferred to winter photoperiods (10 h light, 14 h dark) from two different longer daylengths (14 h or 18 h light daily) in the presence or absence of dim nighttime lighting. Dim nocturnal illumination markedly accelerated adoption of the winter phenotype as reflected in the expansion of activity duration, gonadal regression and weight loss. The two experiments demonstrate substantial efficacy of light intensities generally viewed as below the threshold of circadian systems. Light may act on oscillator coupling through rod-dependent mechanisms.

Analysis of Variance↗

PubMed2003

Photoperiod differentially modulates photic and nonphotic phase response curves of hamsters.

Circadian pacemakers respond to light pulses with phase adjustments that allow for daily synchronization to 24-h light-dark cycles. In Syrian hamsters, Mesocricetus auratus, light-induced phase shifts are larger after entrainment to short daylengths (e.g., 10 h light:14 h dark) vs. long daylengths (e.g., 14 h light:10 h dark). The present study assessed whether photoperiodic modulation of phase resetting magnitude extends to nonphotic perturbations of the circadian rhythm and, if so, whether the relationship parallels that of photic responses. Male Syrian hamsters, entrained for 31 days to either short or long daylengths, were transferred to novel wheel running cages for 2 h at times spanning the entire circadian cycle. Phase shifts induced by this stimulus varied with the circadian time of exposure, but the amplitude of the resulting phase response curve was not markedly influenced by photoperiod. Previously reported photoperiodic effects on photic phase resetting were verified under the current paradigm using 15-min light pulses. Photoperiodic modulation of phase resetting magnitude is input specific and may reflect alterations in the transmission of photic stimuli.

Animals↗

PubMed2003

Melatonin implants disrupt developmental synchrony regulated by flexible interval timers.

Siberian hamsters born into short daylengths near the end of the breeding season are reproductively inhibited from birth and delay gonadal maturation until the following spring. This vernal transition to a reproductive phenotype coincides with an abrupt increase in body weight, and both processes are triggered by an interval timing mechanism that becomes insensitive, or refractory, to short-day inhibition. It was previously demonstrated that hamsters born into simulated natural photoperiods in early August became photorefractory at later ages than hamsters born into September photoperiods. As a consequence of flexibility in the duration programmed by the interval timer, development of seasonal birth cohorts was synchronous with respect to the calendar date simulated by laboratory photoperiod. In the present study, hamsters were born into simulated August or September photoperiods. Hamsters from each cohort were given removable constant release melatonin implants to reversibly obscure the neuroendocrine representation of daylength between 3 and 9 weeks or 9-15 weeks of age. When control hamsters were given beeswax capsules throughout, August-born males were approximately 6 weeks older than September males at the onset of photorefractoriness as assessed by accelerated increases in body weight and testicular size. Females exhibited the same pattern in body weight. These measures were synchronized with respect to calendar date. Synchronization of cohorts was disrupted by melatonin capsules from 3-9 weeks of age but not by later implants. Melatonin implants altered synchronization by influencing the developmental trajectory of September-born hamsters without influencing the August cohort. These results demonstrate that the function of the interval timer underlying photorefractoriness is influenced by photoperiod and by melatonin. The endogenous pattern of melatonin signals adjusts the duration measured by the interval timer to insure that developmental milestones of seasonal cohorts are synchronized with environmental conditions.

Animals↗

PubMed2001

Exotic photoperiods induce and entrain split circadian activity rhythms in hamsters.

The split circadian activity rhythm that emerges in hamsters after prolonged exposure to constant light has been a theoretical cornerstone of a multioscillator view of the mammalian circadian pacemaker. The present study demonstrates a novel method for splitting hamster circadian rhythms and entraining them to exotic light:dark cycles. Male Syrian hamsters previously maintained on a 14-h day and 10-h night were exposed to a second 5-h dark phase in the afternoon. The 10-h night was progressively shortened until animals experienced two 5-h dark phases beginning 10 h apart. Most hamsters responded by splitting their activity rhythms into two components associated with the afternoon and nighttime dark phases, respectively. Each activity component was entrained to this light:dark:light:dark cycle. Transfer of split hamsters to constant darkness resulted in rapid joining of the two activity components with the afternoon component associated with onset of the fused rhythm. In constant light, the nighttime component corresponded to activity onset of the fused rhythm, but splitting emerged again at an interval characteristic for this species. The results place constraints on multi-oscillator models of circadian rhythms and offer opportunities to characterize the properties of constituent circadian oscillators and their interactions.

Animals↗

PubMed2001

A plastic interval timer synchronizes pubertal development of summer- and fall-born hamsters.

Summer and fall decreases in day length induce reproductive regression in adult hamsters and delay reproductive maturation of their young. The following year pubertal development is triggered by an interval timer (IT) that renders animals refractory to inhibitory short day lengths after approximately 25 wk. Timing of gonadal and somatic development was examined among offspring born to Siberian hamsters in early-August vs. late-September day lengths. Pubertal maturation was delayed in both groups until late winter. Gonadal growth occurred at significantly later ages among August- vs. September-born males as did late-winter spurts in ponderal growth of both sexes. Timing of reproductive and somatic development depended on postnatal rather than prenatal photoperiod exposure and was unrelated to the circadian entrainment status of dams. When developmental patterns were assessed in relation to time of year, group differences were largely eliminated. Because the IT triggers these developmental events, its duration must be plastic. This plasticity facilitates a relative synchronization or entrainment of developmental milestones in hamsters born into different late-summer/early-fall photoperiods.

Animals↗

PubMed2001

Daily novel wheel running reorganizes and splits hamster circadian activity rhythms.

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.

Animals↗

PubMed2001

Temporal reorganization of the suprachiasmatic nuclei in hamsters with split circadian rhythms.

A dual oscillator basis for mammalian circadian rhythms is suggested by the splitting of activity rhythms into two components in constant light and by the photoperiodic control of pineal melatonin secretion and phase-resetting effects of light. Because splitting and photoperiodism depend on incompatible environmental conditions, however, these literatures have remained distinct. The refinement of a procedure for splitting hamster rhythms in a 24-h light-dark:light-dark cycle has enabled the authors to assess the ability of each of two circadian oscillators to initiate melatonin secretion and to respond to light pulses with behavioral phase shifting and induction of Fos-immunoreactivity in the suprachiasmatic nuclei (SCN). Hamsters exposed to a regimen of afternoon novel wheel running (NWR) split their circadian rhythms into two distinct components, dividing their activity between the latter half of the night and the afternoon dark period previously associated with NWR. Plasma melatonin concentrations were elevated during both activity bouts of split hamsters but were not elevated during the afternoon period in unsplit controls. Light pulses delivered during either the nighttime or afternoon activity bout caused that activity component to phase-delay on subsequent days and induced robust expression of Fos-immunoreactivity in the SCN. Light pulses during intervening periods of locomotor inactivity were ineffective. The authors propose that NWR splits the circadian pacemaker into two distinct oscillatory components separated by approximately 180 degrees, with each expressing a short subjective night.

Animals↗

PubMed2000

Establishment and persistence of photoperiodic memory in hamsters.

Long summer days unequivocally stimulate, and short winter days inhibit reproduction in Siberian hamsters. By contrast, intermediate-duration day lengths (12.5-14 h long) either accelerate reproductive development or initiate regression of the reproductive apparatus. Which of these outcomes transpires depends on an animal's photoperiodic history, suggesting that hamsters must encode a representation of prior photoperiods. The duration of nocturnal melatonin secretion is the endocrine representation of day length, but nothing is known about how long it takes to establish photoperiodic histories or how long they endure. Hamsters exposed for 2 or more weeks to long summer day lengths acquired a long-day photoperiodic history that determined subsequent reproductive responses to intermediate-duration day lengths and melatonin signals. The memory for long-day lengths persisted in pinealectomized hamsters for 6.5 weeks, faded significantly after 13 weeks, and was functionally absent after 20 weeks. These findings indicate that hamsters are influenced only by relatively recent day lengths and melatonin signals and ignore earlier ones that might cause them to misinterpret the salience of current day lengths.

Analysis of Variance↗

PubMed1998

Melatonin chimeras alter reproductive development and photorefractoriness in Siberian hamsters.

Nightly melatonin (MEL) durations > 8 h provoke gonadal regression and decreases in body mass, whereas signals < 7 h stimulate gonadal and somatic growth in male Siberian hamsters. The authors sought to determine the minimum frequency of short MEL signals sufficient to induce the long-day phenotype in several photoperiodic traits. D,L-propranolol (hereafter propranolol) injections shortened MEL signals on the night of treatment without altering MEL on the subsequent night; this permitted interpolation of short MEL signals at variable frequencies against a background of long MEL signals (chimeras). Hamsters kept in short days (10 h light/day, 10L) were injected with propranolol 6 h after dark onset for 28 consecutive weeks beginning at 30 days of age (Week 0) either every other day or once every 3, 6, or 9 days. Control animals were injected with saline or with propranolol during the light phase or were transferred to long days (16L) at Week 0. Hamsters in 16L underwent rapid gonadal development and increases in body mass and displayed summer pelage color, as did hamsters treated with propranolol every other day. Animals treated with propranolol less frequently than every other day uniformly maintained undeveloped gonads and winter-like body weights, but pelage color became proportionately darker with increased frequency of propranolol treatments. The onset of spontaneous testicular development in 10L was unaffected by propranolol injections. After termination of injections at Week 28, testicular regression was not observed in most 10L animals that previously had undergone spontaneous testicular development; however, 40% of hamsters that had been injected with propranolol every 3rd night did manifest the winter phenotype after Week 28. In an alternating sequence, short MEL signals completely override long signals and induce the summer phenotype. Threshold frequencies differ for MEL stimulation of long-day pelage and gonadal phenotypes. The timing and development of refractoriness to MEL does not depend in any simple manner on the number of long MEL signals or on the accumulation of a reaction product produced by long, and depleted by short, MEL signals.

Adrenergic beta-Antagonists↗

PubMed1997

Pattern of change in melatonin duration determines testicular responses in Siberian hamsters, Phodopus sungorus.

The impact of photoperiodic history was studied in male hamsters kept from birth to 6 wk of age (Week 0) in long-day (LD; 16 h light per day) or short-day (SD; 10 h light per day) photoperiods. At Week 0, hamsters were transferred to constant light and were s.c. infused daily with melatonin (MEL; 4 ng/h) until Week 12. Groups of SD hamsters received 10-h MEL infusions or MEL infusions of durations that decreased linearly by 1-2 min/day from 10 h at Week 0 to 7.5 h at Week 12. LD hamsters were infused for 5 h/day or in patterns that decreased from 10 to 7.5 h or increased from 5 to 7.5 h during Weeks 0-12. MEL signals of decreasing duration produced opposite effects on the gonads of LD and SD hamsters: decreasing MEL durations induced complete gonadal regression in LD hamsters (testis weight = 42 +/- 3 mg) but stimulated testis growth in SD hamsters (testis weight = 276 +/- 57 mg; p < 0.05). MEL infusions that were of shorter but increasing duration induced gonadal regression in LD hamsters. The present experiments indicate that MEL signals of a given sequence and duration can produce either gonadal growth or regression depending on the hamster's photoperiodic history. The pattern of change in MEL secretion, as well as absolute duration of the MEL signal, is important for implementing seasonal cycles of reproduction.

Animals↗

PubMed1997

Environmental induction of photononresponsiveness in the Siberian hamster, Phodopus sungorus.

In seasonally breeding rodent species, a fraction of the population is unresponsive to short day lengths (DL) and remains reproductively competent during winter. We previously observed that incidence of nonresponsiveness to short days was affected by photoperiodic history. Here we tested whether exposure to long DL (18 h light/day; 18L) renders animals unresponsive to short DL (10L). Hamsters, maintained from birth in 10L, were transferred at week 6 to 18L or 14L. Ten weeks later (week 16), groups were transferred to 10L for 10 wk. All hamsters maintained in short DL from birth had undeveloped testes at week 6. At week 26, however, 92% of hamsters previously kept in 18L failed to undergo complete gonadal regression in 10L, compared with only 10% of hamsters previously in 14L. Entrainment of locomotor activity in 10L in nonresponsive hamsters resembled that typically observed under long DL. Exposure to 18L may induce nonresponsiveness by altering interactions of component circadian oscillators that mediate gonadal regression in short DL.

Aging↗

PubMed1997

Photoperiodism in hamsters: abrupt versus gradual changes in day length differentially entrain morning and evening circadian oscillators.

In studies of photoperiodism, animals typically are transferred abruptly from a long (e.g., 16 h light per day [16L]) to a short (8L) photoperiod, and circadian oscillators that regulate pineal melatonin secretion are presumed to reentrain rapidly to the new photocycle. Among rats and Siberian hamsters, however, reentrainment rates vary depending on whether additional darkness is added to morning or evening, and a subset of hamsters (nonresponders) fails ever to reentrain normally to short photoperiods. The authors assessed whether several short-day responses occurred at different rates when darkness was extended into morning versus evening hours and the effectiveness of abrupt versus gradual shortening in day lengths (DLs). Entrainment patterns of photoresponsive hamsters also were compared to those of photononresponsive hamsters. Responsive hamsters transferred on a single day from 16L to 8L underwent more rapid gonadal regression, weight loss, decreases in follicle-stimulating hormone titers, and expansion of nocturnal locomotor activity when darkness was added to morning versus evening. When the dark phase was extended gradually by 8 h over 16 weeks, short-day responses occurred at the same rate whether darkness was appended to morning or evening or was added symmetrically. Darkness added to evening promoted more rapid short-day responses when it was added gradually rather than abruptly, despite the fact that average DLs were significantly shorter for the latter group. Among nonresponders, morning extensions of darkness transiently increased activity duration, whereas evening extensions did not. Gradual and abrupt decreases in DL differentially affect entrainment of evening and morning circadian oscillators. The authors argue for the incorporation of simulated natural photoperiods in studies of photoperiodism.

Animals↗

PubMed1996

Three daily melatonin infusions alter gonadal development but not GnRH neuron number in the medial preoptic area or diagonal band of Broca in Siberian hamsters.

Among juvenile Siberian hamsters reproductive development is associated with an increased number of unipolar GnRH-immunoreactive neurons in the diagonal band of Broca and medial preoptic area. In the present study, GnRH neuron morphology was assessed in male juvenile hamsters which were treated with three daily melatonin (MEL) infusions to initiate or delay gonadal development. Hamsters gestated in short days were transferred to constant light (LL) at day 14 of age and infused on days 18-20 with MEL for 6 h/day. This treatment stimulated testis development compared to that in saline-infused controls. By contrast, testis growth was suppressed by three 12 h MEL infusions in long-day gestated hamsters in LL from day 14. The number of unipolar and bipolar GnRH neuron subtypes was the same irrespective of MEL infusion or preweaning photoperiod. Thus, gonadal response to three MEL infusions is independent of changes in GnRH neuron number.

Animals↗

PubMed1996

Enhanced reproductive responses to melatonin in juvenile Siberian hamsters.

Reproductive responses to melatonin (Mel) exposure were assessed in male Siberian hamsters gestated in long (16 h light/day; 16L) or short (8 h light/day; 8L) day lengths (DLs). Hamsters were maintained in constant light beginning at 14 days of age (day 14) and were infused for 3 successive days beginning on day 18, 25, or 32 with long (12 h/day) or short (6 h/day) durations of Mel or saline. Two weeks later, testis and body weights were determined. Responsiveness to Mel was enhanced in hamsters beginning shortly after weaning and was influenced by photoperiodic history. Gonadal growth in 16L hamsters was inhibited by 12-h Mel infusions initiated on day 18 or day 25, but infusions initiated on day 32 were ineffective. Hamsters gestated in 8L were not responsive to Mel treatments initiated on day 18, but discriminated 12-h from 6-h infusions at day 25 and manifested reduced gonadal growth after 12-h Mel infusions on day 32. Hamsters born in 8L to dams judged as photoinsensitive to short DLs did not respond to 12-h infusions on day 32 as inhibitory signals. We propose that maternal Mel secretion provides juvenile males with a photoperiodic history, which allows them to compare gestational with early postweaning Mel signals and thereby program seasonally appropriate developmental trajectories.

Aging↗

PubMed1995

Seasonal adaptations of Siberian hamsters. I. Accelerated gonadal and somatic development in increasing versus static long day lengths.

Studies of rodent photoperiodism have almost exclusively employed fixed photoperiods with abrupt shifts in day length (DL) of 4-8 h effected in a single day. Because DLs in nature change continuously and incrementally, rates of gonadal and somatic development were compared in the present study in hamsters exposed to gradually increasing vs. fixed DLs. Male hamsters gestated in 12 h light/day (12L) and exposed to DLs that increased gradually from 12L to 15.5L (experiment 1) or from 12L to 16L (experiment 2) weighed more and had larger gonads than did hamsters gestated and maintained from birth in a DL of absolutely greater duration (16L). Gradual increases in DL from 10L to 12L also resulted in more rapid somatic development than did gestation and maintenance in a static 12L photoperiod. The pattern of gradual increases in DL was not sufficient to accelerate development at all DLs but was effective in the range of 12L to 19L. Siberian hamsters are responsive to the pattern of photoperiodic change; the maximally stimulatory photoperiodic stimulus is not a fixed long day, but is instead increasing DLs, even those with absolutely shorter photophases; short gestational DLs potentiate the effects of longer postnatal DLs. The relations heretofore elaborated between fixed DLs and physiological responses differ from those obtained with more natural photoperiodic transitions.

Adaptation, Physiological↗

PubMed1995

Seasonal adaptations of Siberian hamsters. II. Pattern of change in daylength controls annual testicular and body weight rhythms.

Studies of rodent photoperiodism almost without exception have employed fixed day lengths (DLs) and abrupt transitions from long to short DLs. Because the natural progression of changes in DL carries predictive information and may have physiological consequences, we determined seasonal fluctuations in testis size and body weight in Siberian hamsters maintained in a year-long pattern of increasing and decreasing DLs. A cycle of gonadal development, regression, and recrudescence, and corresponding changes in body weight, were observed in hamsters maintained in separate simulated natural photoperiods (SNPs) in which DLs neither fell below nor exceeded the putative critical DL of 13 h. Gradually decreasing DLs as long as 15.3 h induced gonadal regression, and DLs as short as 12.3 h supported ponderal growth, depending on the hamster's prior photoperiodic history. DLs experienced by hamsters during development influenced the adult incidence of responsiveness to short DLs. Photorefractoriness to short DLs occurred earlier in hamsters kept in static 10-h than in 12-h DLs. Increasing DLs in winter had little impact on the rate of gonadal recrudescence and weight gain. These data extend earlier investigations in showing the photoperiodic history determines gonadal responses over a broad range of DLs and influences gonadal responsiveness to short DLs and the triggering of the interval timer underlying recrudescence.

Adaptation, Physiological↗

PubMed1995

Testicular regression and recrudescence without subsequent photorefractoriness in Siberian hamsters.

Adult male Siberian hamsters transferred from 16 h light/day (16L) to 14 h light/day (14L) underwent gonadal regression and recrudescence over the course of 24 wk; the duration of reproductive quiescence was shorter by 10 wk than in hamsters transferred from 16L to 10L. A decrease in day length (DL) at week 12 from 14L to 10L greatly extended the duration of testicular involution, whereas transfer at week 12 from 10L to 8L was without effect. Hamsters that had manifested gonadal regression and recrudescence in 14L immediately initiated a second regression when challenged with 10L. Intermediate DLs induce gonadal regression and recrudescence without rendering hamsters refractory to shorter DLs. Intermediate DLs sufficient to initiate gonadal regression may be too long to trigger the interval timer that eventually induces refractoriness to shorter DLs and may be successively interpreted as short and long days, respectively, by Siberian hamsters.

Animals↗

PubMed1995

Long-term reproductive effects of a single long day in the Siberian hamster (Phodopus sungorus).

Testicular regression was prevented or attenuated in Siberian hamsters exposed to a single 1- to 4-h extension of the 16-h photophase at 18 days of age and subsequently maintained in a short photoperiod (8L:16D) through Day 35. Testicular weights on Day 35 were not correlated with the duration of the active phase of wheel running or with the time of activity onset after transfer to the 8L:16D photoperiod. Wheel-running activity was not stably entrained to the light-dark cycle by 35 days of age. Progonadal effects of a single 33-h light pulse were greatest at 18 days of age, still evident at 30 days, but undetectable in older hamsters. In female hamsters, a single longer day at weaning was associated with increased fecundity several weeks later. Long photoperiods accelerated development of antral ovarian follicles, but exposure to males was necessary to induce ovulation before 60 days of age. The interval beginning shortly after weaning is one of heightened responsiveness to changes in day length (DL); exposure to increasing DL at this time may prolong the breeding season when DL decreases after the summer solstice. We suggest that the long-term effects of acute light treatments on reproduction are mediated by sustained changes in melatonin secretion induced by reprogramming of circadian oscillators.

Aging↗