Biomedical subjects

R E Mistlberger

Publications and source records attributed to R E Mistlberger.

54 records · Page 3Linked to original sources

PubMed1992

Ethanol and circadian rhythms in the Syrian hamster: effects on entrained phase, reentrainment rate, and period.

Wheel-running rhythms were examined in male hamsters with access to 28% ethanol in lieu of water. One group was recorded in a light-dark (LD) cycle that was phase advanced by 8 h on three occasions separated by 23-27 days. On two of the three occasions, hamsters were subjected to a 2- to 3-h cage change procedure designed to stimulate wheel running, which accelerates the rate of reentrainment to 8-h advances. Ethanol and control hamsters showed no group differences in rhythm amplitude, entrained phase, or reentrainment rate. Both groups showed faster reentrainment in the cage change condition. A second group of hamsters recorded in constant dim showed a small but significant lengthening of the free-running period of their wheel-running rhythm when provided with a 28% ethanol solution. Wheel running decreased during ethanol access in this group. Voluntary ethanol consumption evidently can slow the circadian pacemaker regulating activity rhythms in hamsters but has no measurable effect on photic entrainment or pacemaker response to LD shifts or nonphotic manipulations (stimulated activity). Period lengthening may be secondary to decreased activity, but other period-activity correlations obtained did not reveal a strong association between these two variables.

Alcohol Drinking↗

PubMed1992

Nonphotic entrainment of circadian activity rhythms in suprachiasmatic nuclei-ablated hamsters.

This study examined the role of the suprachiasmatic nuclei (SCN) in nonphotic entrainment. The wheel-running activity of SCN-ablated hamsters was recorded in constant dark (DD) and then under prolonged schedules of 2-hr daily cage changes, restricted food availability, and daily light-dark (LD) cycles. Some hamsters with very large lesions subsuming the SCN and surrounding areas exhibited significant, albeit unstable, circadian activity rhythms in DD. Some hamsters with similar ablations also showed entrained rhythms to daily cage change schedules. All hamsters showed robust rhythms entrained to a daily feeding schedule, but no hamsters showed entrainment to LD cycles. Competent circadian oscillators evidently exist outside the SCN, at least 0.5 mm or more away, and at least some are nonphotically entrainable. Weaker entrainment in animals with larger lesions suggests that nonphotically entrainable oscillators also exist within the SCN or its immediate vicinity.

Animals↗

PubMed1992

Anticipatory activity rhythms under daily schedules of water access in the rat.

Rats anticipate a fixed daily feeding time by entrainment of a component of their multioscillatory circadian system. The range of stimuli capable of entraining this component is little studied. Previous studies suggest that restricted water access is not an effective entrainment stimulus, as measured by general locomotion. The present study re-examined the issue, using two other measures of activity: wheel running and activity at a food-water delivery bin. Rats restricted to 1 hr of water each day in the middle of the light and to food in the 12-hr dark period showed no anticipation of this event in the wheel-running measure, but some rats did show anticipation in the delivery bin activity measure. Rats (bin activity measure only) restricted to 1 hr of water and 1 hr of food separated by intervals of 7, 10, or 12 hr, in either the light or the dark, showed consistent anticipation of food access time but little or no anticipation of water access time. Water access time also did not sustain food anticipatory rhythms in animals whose food-water schedules were reversed. However, deprivation of water or of both food and water for 72 or 90 hr was usually associated with specific increases in bin activity at both the usual feeding and drinking times. Water access, like food, appears to provide cues capable of entraining an anticipatory circadian mechanism. Differences in the type and amount of anticipatory activity preceding these events may reflect differences in the strengths of the two entrainment cues and/or in the activity levels or specific behavioral strategies promoted by hunger and thirst.

Animals↗

PubMed1991

The benzodiazepine triazolam phase-shifts circadian activity rhythms in a diurnal primate, the squirrel monkey (Saimiri sciureus).

Triazolam can shift the phase of circadian rhythms in hamsters recorded in constant light or dark. This effect is apparently mediated by physical activity stimulated by the drug. We examined whether triazolam can shift the phase of circadian rhythms in a diurnal primate, the squirrel monkey, that is sedated by triazolam. Single injections of triazolam at 0.15-0.20 mg/kg induced phase advances or delays of monkey activity rhythms recorded in constant light. The phase-response curve is similar to that obtained for hamsters. Behavioral activation is evidently not necessary for a phase-shifting action of triazolam in this primate. A companion study in which triazolam was administered to squirrel monkeys in the dark in a light-dark cycle reentrainment paradigm failed to find evidence for a phase shifting action of triazolam. Shifts induced by triazolam in monkeys recorded in constant light may thus reflect changes in light exposure as a consequence of sedation or altered retinal processing of light.

Animals↗

PubMed1991

Scheduled daily exercise or feeding alters the phase of photic entrainment in Syrian hamsters.

Single daily bouts of appropriately timed activity can phase-shift or entrain circadian rhythms in rodents maintained in constant dark (DD). Whether this apparent feedback of behavioral activity to the circadian pacemaker has any adaptive significance in nuclear; circadian rhythms are normally entrained by light-dark (LD) cycles, and this may override any effects of activity. To address this issue, the phase of entrainment to LD cycles was examined in hamsters exposed to a daily exercise schedule (3 h of induced wheel running). Hamsters exercised late in the dark showed a significant delay of entrained phase in LD (i.e., they became relative "night owls") and lengthening of free-running periodicity in DD, compared to controls and hamsters exercised in midlight. Hamsters fed in midlight (arousal without wheel running) showed a significant advance of LD entrained phase (i.e., they became "early birds"). These observations provide the necessary rationale for further examination of the functional significance of behavioral feedback for the normal entrainment process. In addition, they rise the possibility that the entrained phase of human circadian rhythms can be similarly manipulated by behavioral procedures such as timed exercise.

Animals↗

PubMed1991

Effects of daily schedules of forced activity on free-running rhythms in the rat.

Circadian rhythms of hamsters can be phase-shifted or entrained by single or daily sessions of induced wheel running. In contrast, observations of rats under restricted-feeding schedules suggest that their free-running rhythms are not readily entrainable by a daily bout of intense activity. A formal test of this idea was made by subjecting rats to daily 2-hr or 3-hr sessions of forced treadmill activity. None of 18 rats entrained to a daily treadmill schedule when tested in constant dim light, but 1 of 16 did entrain when tested after blinding, when the period of its free-running activity rhythm was very close to the period of the treadmill schedule and when the onset of its daily active phase overlapped with the treadmill sessions. These conditions were recreated in a final group of eight rats; the rats were trained in a light-dark cycle, blinded, and subjected to a treadmill schedule with a period of 23.91 hr that was initiated at the onset of the rats' active phase on day 1. Six of these rats entrained. The mechanism for entrainment by activity schedules clearly exists in rats, but the conditions under which this occurs are highly constrained, suggesting that activity is a very weak zeitgeber in this species. It is argued that the evolution of functionally separable food- and light-entrainable oscillators in the rat demands a very low sensitivity to feedback effects of activity.

Animals↗

PubMed1990

Food-anticipatory rhythms under 24-hour schedules of limited access to single macronutrients.

Food-restricted rats anticipate a fixed daily mealtime by entrainment of a circadian timekeeping mechanism separate from that which generates daily light-entrainable activity rhythms. The entrainment pathways and rhythm-generating substrates for food-anticipatory rhythms are unknown. In this study, we attempted to define minimal food-related stimuli necessary or sufficient for food anticipation by employing schedules of restricted macronutrient availability, with or without free access to a complementary diet. Rats did not anticipate a daily meal of protein, carbohydrate, or fat, as measured by tilt-cage, running-wheel, or food-bin activity, when they had free access to other nutrients. However, rats did anticipate single-macronutrient meals when they were limited to only two, larger, complementary meals each day (protein-fat, protein-carbohydrate) providing a reduced total number of calories. Previous work has shown that caloric restriction per se is not a prerequisite for food anticipation. In combination with that study, the present results indicate that the size of a nutrient meal, in absolute terms or relative to total daily nutrient intake, is of pre-eminent importance in determining its value as a synchronizer of anticipatory rhythms. The results further suggest that physiological responses unique to the ingestion and absorption of any particular macronutrient are not necessary components of the entrainment pathway.

Animals↗

PubMed1990

Characteristics of food-entrained circadian rhythms in rats during long-term exposure to constant light.

Rats possess a system of circadian oscillators that permit entrainment of circadian activity rhythms independently to 24 hr cycles of light-dark and food access. The nature of interactions between food- and light-entrainable oscillators was examined by observing the generation and persistence of food-entrained circadian rhythms in rats whose light-entrainable rhythms were eliminated by long-term exposure to constant light. Most of these rats showed a delayed generation of food-entrained rhythms and only one of eight animals showed persistence of food associated rhythms during a 4-day food deprivation test. Rats whose light-entrainable rhythms are eliminated by suprachiasmatic nuclei ablation show, in contrast, normal generation and persistence of food-entrained rhythms. The results suggested a disruptive influence of constant light on non-photic entrainment, possibly due to coupling forces between damped light-entrainable oscillators and the food-entrainable oscillators.

Animals↗

PubMed1988

Daily hoarding opportunity entrains the pacemaker for hamster activity rhythms.

The effects on activity rhythms of a daily 30 min opportunity to leave the home cage and hoard seeds from an open field were assessed in Syrian hamsters housed in continuous dim illumination. Six of ten hamsters responded with clear entrainment of their activity rhythms to the hoarding opportunity, as demonstrated by responses to phase shifts and by the onset phase of subsequent freerunning rhythms. No entrainable component separate from the freerunning rhythm was ever observed. Two hamsters showed phase shifts in response to the hoarding opportunity, but they did not meet the criteria for stable entrainment, and two did not respond with noticeable changes in rhythmicity. Ablations of the suprachiasmatic nuclei (SCN) were attempted in three hamsters that had entrained stably to the hoarding time. The effects of partial lesions in two animals indicated that the entrained rhythm was controlled by the light-entrainable pacemaker represented by the SCN. The one animal with an apparently complete lesion, however, developed a clear, but irregular, increase in activity in anticipation of the daily hoarding time. SCN ablation apparently unmasked an oscillator system separate from the SCN and susceptible to entrainment by a nonphotic cue. The oscillator mechanism affected by daily hoarding opportunities in hamsters appears to be tightly coupled to the SCN pacemaker, in contrast to the system in rats that is synchronized by daily feeding schedules.

Animals↗

PubMed1987

Period-amplitude analysis of rat electroencephalogram: stage and diurnal variations and effects of suprachiasmatic nuclei lesions.

Period-amplitude analysis was used to measure the number of waves per unit time (wave incidence) and wave amplitude for 19 wavelength categories in the lateral cortical electroencephalogram (EEG) of five intact and four suprachiasmatic nuclei-lesioned rats during NREM sleep, waking, and paradoxical sleep (PS) over a period of 24 h. The analysis confirmed several parallels between rat electroencephalogram (EEG) and human EEG: The wave incidence and amplitude at all wavelengths are both practically indistinguishable between wake, PS, and NREM sleep onset. As NREM sleep EEG amplitude increases, slow wave incidence and amplitude increase. The incidence and amplitude of slow waves are greatest at the start of the diurnal NREM sleep period and lowest at its end. The pattern of diurnal variation of the NREM EEG may be modeled using two wave generators (sources of variation), one between 1 and 4 Hz, and the other between 5 and 16 Hz. The diurnal patterns for wake and PS are less clear, but both appear to require three generators, one below 3 Hz, one between 3.5 and 6 Hz, and one above 9 Hz. The EEG of suprachiasmatic nuclei-lesioned rats does not show any shift to longer wavelengths in NREM sleep. Wake, PS, and NREM EEG in these rats have a lower incidence and amplitude of slow waves than the corresponding stages in intact rats. One explanation is an inhibition of the slow wave generator as a result of the lesions.

Animals↗

PubMed1987

Relationships among wake episode lengths, contiguous sleep episode lengths, and electroencephalographic delta waves in rats with suprachiasmatic nuclei lesions.

The lengths of sleep and wake episodes during 2 consecutive days of recording were measured in five rats lacking circadian rhythms owing to lesions of the suprachiasmatic nuclei. Total sleep (TS) episode lengths and the amount of NREM sleep and paradoxical sleep (PS) within each episode were examined in relationship to the lengths of the immediately preceding and the immediately following wake episodes. As putative measures of sleep intensity, average and maximum delta wave (1-4 Hz) incidence and amplitude within NREM were also examined in relation to adjacent wake episode lengths. For sleep episodes longer than 50 min (78% of daily sleep), TS episode lengths and amount of NREM within these episodes showed significant positive correlations with both prior and subsequent wake episode lengths. PS durations within sleep episodes also showed significant positive correlations with subsequent wake episode lengths, but little correlation with prior wake episode lengths. The results suggest that in the absence of sleep-wake circadian rhythms, sleep time is subject to short-term homeostatic regulation. Amounts of PS within sleep episodes were highly correlated (r = 0.84) with amounts of NREM. NREM delta wave incidence and amplitude showed no significant relationships with the lengths of prior or subsequent wake episodes, suggesting that variations in sleep intensity may not play a prominent role in the short-term homeostatic regulation of ad lib sleep. Delta wave incidence and amplitude were also not correlated with the duration of NREM episodes, but incidence during wake was positively correlated with wake episode duration, suggesting that delta density during wake may be an electrophysiological indicator of the propensity to sleep.

Animals↗

PubMed1986

Carbachol phase shifts circadian activity rhythms in ovariectomized rats.

Ovariectomy in the rat abolishes alpha-bungarotoxin (alpha-BTX) binding within the suprachiasmatic nucleus (SCN), a putative circadian pacemaker, and markedly reduces cholinergic activation of SCN cells. Circadian rhythms of running wheel activity were monitored continuously in intact male and female and chronically ovariectomized rats before and after intraventricular carbachol injections. Carbachol produced similar phase shifts of the free-running rhythms in all groups. The results suggest that carbachol can influence the circadian system of rats by activation of cholinergic receptor sites independent of those binding alpha-BTX within the SCN.

Animals↗

PubMed1985

Periodic water availability is not a potent zeitgeber for entrainment of circadian locomotor rhythms in rats.

Entrainment of tilt-cage measured circadian activity rhythms to a 2 hr daily period of water availability was assessed in rats fed either an oil-chow mash, which rats readily consume in the absence of water, or dry pellet chow, which rats less readily consume in the absence of water. Four of 6 pellet fed rats but only 2 of 14 mash fed rats exhibited entrainment to water access. Periodic water availability, unlike periodic food availability, thus does not appear to be a potent zeitgeber for circadian activity rhythms in the rat. The entrainment that does occur in some rats may result from shifting of food intake to coincide with the availability of water.

Animals↗

PubMed1984

Recovery of anticipatory activity to restricted feeding in rats with ventromedial hypothalamic lesions.

Entrainment of circadian activity rhythms to a fixed daily mealtime was measured in intact and ventromedial hypothalamic (VMH) lesioned rats housed in tilt-cages. Intact rats showed a clear increase in activity for 2-3 hr prior to the 2 hr daytime feeding period. Anticipatory activity in lesioned rats was attenuated or absent during restricted feeding 5-9 weeks after surgery, but was evident in all rats, even those bearing apparently total VMH damage, during a second restricted feeding schedule 14-21 weeks after surgery. These results show recovery of function and argue against a necessary role for the VMH in food entrained rhythms.

Animals↗

PubMed1984

Suprachiasmatic nuclei lesions eliminate circadian temperature and sleep rhythms in the rat.

We conducted a long-term study of the circadian rhythms of temperature and sleep in the rat after lesions of the suprachiasmatic nuclei (SCN). Brain temperature was measured with thermistors and sleep-wake was scored on the basis of continuously recorded EEG using a computerized system. Rats with complete SCN lesions did not exhibit circadian rhythms in constant dim illumination. Rats with partial SCN lesions generated weak and variable free-running rhythms, and when exposed to a light-dark cycle, some showed a reduced amplitude and altered waveform relative to normal rats. A few rats with partial SCN lesions showed a recovery of function. There was little difference between the circadian rhythms in temperature and waking, and these measures responded similarly to all lesions. Thus, no support was found for the notions that anatomically distinct oscillators control the circadian rhythms of temperature and activity, or that an oscillator outside of the SCN controls the circadian rhythm of temperature.

Animals↗

PubMed1983

Recovery sleep following sleep deprivation in intact and suprachiasmatic nuclei-lesioned rats.

Recovery sleep was studied for 3-5 days following 24 h of sleep deprivation (TSD) in normal rats and in rats lacking circadian rhythms (CRs) of sleep because of prior lesioning of the suprachiasmatic nuclei (SCN). One group of lesioned rats was run in constant dim light. Another lesioned group and an intact group were run on a 12:12 dark-light schedule with TSD and recovery beginning at lights-off. All groups showed immediate rebounds of high-amplitude NREM sleep and paradoxical sleep, confined mostly to the first 12-18 h of recovery, and decreases in moderate and low-amplitude NREM sleep during the first 6-12 h of recovery. Thus, sleep stage rebound priorities were little affected by CRs. Total sleep rebound was initially greatest in intact rats, but limited mostly to the first 12 h of recovery. Total sleep rebound was distributed over a longer period in SCN rats, but total accumulated rebound was similar in all groups. Thus, CRs appear to modulate the timing but not the amount of accumulated total sleep rebound. Results were interpreted in terms of ceiling effects on total sleep, delayed rebounds, and competition between CRs and homeostatic recovery processes. Recovery sleep of lesioned rats on the dark-light schedule was marked by a transient diurnal rhythm.

Animals↗

PubMedDate not supplied

Effects of aging on food-entrained circadian rhythms in the rat.

Twenty-four hour schedules of restricted food availability entrain a component of the circadian activity rhythm in rats via a food-entrainable pacemaker separate from the light-entrainable pacemaker. The effect of aging on food-entrained circadian rhythms was examined in 6 rats maintained on a restricted diurnal feeding schedule from age 3-21 months and again from 24-25 months. Food-entrainment, measured as behavioral anticipation of a 1-hr daily mealtime during the middle of the light period and persistence of this anticipation rhythm during food deprivation, was apparent in the aged rats when recorded in wheel-running cages from 20-21 months of age. Despite the long duration of restricted diurnal food diurnal food access, the aged rats, like young rats, rapidly to nocturnal activity when transferred to ad lib feeding. When restricted diurnal feeding was reinstated at 24 months age, these rats, now recorded in food-bin monitoring cages, required more time for a food anticipation pattern to emerge and showed a lower amplitude food anticipation rhythm compared to a group of young adult rats. These age-related changes are similar to those that characterize photically entrained circadian rhythms and suggest that both components of the rat's multioscillatory circadian timekeeping system deteriorate in parallel over the life span.

Aging↗

PubMedDate not supplied

Circadian rhythms of activity and drinking in mice lacking angiotensin II 1A receptors.

Angiotensin II (ANG II) type 1 receptors are found in the mouse suprachiasmatic nucleus (SCN), the site of the circadian pacemaker, but their significance for circadian timekeeping is unknown. We examined circadian rhythms of wheel running and drinking in angiotensin AT(1a) receptor knockout (KO) mice. Mean daily running and drinking activity were elevated in KO mice under a light-dark (LD) cycle and in constant dark (DD). These increases were confined to the usual active (dark) period, thus, the 'amplitude' of running and drinking rhythms was higher in KO mice. The phase of entrainment to LD (measured by the onset of the daily active period) did not differ between groups, either in LD or on the first day of DD ('unmasked' phase). KO mice showed a modestly shorter free-running period (tau) in DD. The direction and magnitude of phase shifts to light pulses at two circadian times (CTs) in DD did not differ between groups. Core functions of the circadian system appear intact following AT(1a) receptor KO. The modestly shorter tau and increased rhythm amplitude in KO mice may be secondary to an effect of the mutation on the level of running and drinking activity.

Animals↗