The effect of a hyperdynamic environment on the development of the rat retina.
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Biomedical subjects
Publications and source records attributed to C A Fuller.
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To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of our results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.
This study examines the hypothalamic temperature rhythm and its relationship with the colonic temperature rhythm of squirrel monkeys in 24-h light-dark cycles (LD 12:12) at four different ambient temperatures (Ta). The waveforms and phases of both temperature rhythms were similar in all TaS. The rhythm amplitudes were, however, reduced as Ta increased. The 24-h means also showed systematic decreases at higher TaS. The hypothalamic temperature was regulated over a narrower range than the colonic temperature and was higher than colonic temperature at all TaS except the warmest. Further, the mean nighttime temperatures were influenced more by Ta than were the mean daytime temperatures. In summary, the hypothalamic and colonic temperature rhythms are very similar in their circadian regulation. However, the mean temperature levels of these rhythms are controlled differentially. Thus these rhythms are the integrated response of both the circadian and thermoregulatory control systems.
This study was designed to examine the possible effects of hyperdynamic fields (+G) on the circadian timekeeping system of the squirrel monkey. Eight monkeys were sequentially exposed to 1.0, 1.5, 2.0 and 1.0 G. During the two 1 G phases and the 2.0 G phase, the animals were exposed to constant light (LL) in addition to the 24-hr light-dark cycle (LD 12:12) present during the rest of the experiment. All animals were housed simultaneously on an 18 ft diameter centrifuge. The animals were allowed food and water ad lib, the intake of which was monitored electronically every 30 minutes. In all three acceleration fields, the animals demonstrated prominent circadian rhythms in both feeding and drinking. In the LD cycle, both rhythms were entrained with 24 hr periods. A phase delay occurred between the rhythms and the LD synchronizer in the +G environment. Moreover, when the animals were exposed to LL at 2.0 G, the mean free-running period was longer than when the animals were at 1 G either before or after the hyperdynamic exposure. In summary, this study demonstrates that the circadian timekeeping system of these primates is functional in the hyperdynamic environment, however, some of its components appear to be regulated at different homeostatic levels.
Cephalic fluid shifts, induced by lower body positive pressure (LBPP) are known to influence various physiological systems (i.e. cardiovascular and renal). In earlier experiments, we observed an apparent change in the arousal state of primates in such LBPP conditions. This study was designed to examine the effects of LBPP on arousal state and body temperature level which is normally correlated with sleep. Chair restrained male squirrel monkeys were exposed to 40 mmHg LBPP for 90-100 minutes between the daytime hours of 13:00-15:00. Each monkey was placed in a specially modified restraint chair to which they were highly restrained [correction of trained]. Deep body temperature (DBT) was collected from 10 animals. Sleep parameters were obtained from 6 animals chronically implanted for sleep recording. A video camera was used to observe each animal's apparent state of arousal. LBPP resulted in an approximate 0.9 degree C decrease in DBT. During video observation some animals appeared drowsy during LBPP, however, sleep recording revealed no significant changes in the state of arousal. Thus, LBPP is capable of inducing a mild hypothermia [correction of hyperthermia]. Further, the mechanisms underlying the observed lowering of body temperature appear to be independent of arousal state.
This study examined the responses of small primate, the squirrel monkey, to acute exposures to hyperdynamic environments. Body temperature, heart rate, and behavior of four restrained squirrel monkeys were recorded. After baseline monitoring at 1 G, monkeys were exposed to: a) +2 Gz for 60 min, b) a hyperdynamic profile simulating the gravitational envelope of the space shuttle during launch (8 min, +2.9 Gz max), or c) a simulated shuttle re-entry profile (19 min, +1.7 Gz max). In all experiments, the colonic temperature started to fall within 10 min of the onset of centrifugation and declined by as much as 2 degrees C in some conditions. This was in contrast to the stable body temperature observed during the baseline period. Also, the heart rate showed distinct elevations during centrifugation. Heart rate subsequently declined to baseline levels during the post-centrifugation phase. Behaviorally, after the onset of centrifugation, the animals periodically appeared to become drowsy and fall asleep. On the other hand, during the control period they tended to be alert, shifting their gaze about the cage. Thus, primates are susceptible to acute exposures to hyperdynamic fields, demonstrating significant physiological and behavioral changes.
In the absence of other environmental cycles, daily variations in auditory stimuli are normally not capable of entraining the circadian rhythms of drinking behavior in the squirrel monkey (Saimiri sciureus). However, the drinking rhythm appears to become entrainable by previously ineffective auditory cues after lesions are placed which destroy only the caudal portion of the hypothalamic suprachiasmatic nuclei. The results suggest specificity of function within the SCN and an increased influence of auditory stimuli in animals with impaired SCN function.
Many panting mammals can cool the brain below body core temperature during heat stress. Studies on human subjects suggest that primates may also be able selectively to regulate brain temperature. We examined this possibility by measuring hypothalamic (Thy) and colonic (Tco) temperatures of unanesthetized squirrel monkeys (Saimiri sciureus) in two different experiments. First, Thy and Tco were examined at four different ambient temperatures (Ta) between 20 and 36 degrees C. Over this range of Ta, Thy was regulated within a narrower range than Tco. In the cold Ta, Tco was lower than Thy; whereas in warm Ta, Tco was higher than Thy. Second, monkeys maintained at 35 degrees C Ta were acutely exposed to cool air blown on the face or abdomen. Air directed at the face cooled Thy more and faster than Tco, whereas air directed at the abdomen cooled Tco and Thy at the same rate. The second experiment was repeated in anesthetized animals with a thermocouple in the right atrium, and the results showed that this brain cooling was not produced by cooling of blood in the body core. These data demonstrate that the squirrel monkey is capable of selectively regulating Thy. Further the results suggest that venous blood returning from the face may be involved in selective brain cooling in warm environments.
To examine the role that the phasic and tonic aspects of the light-dark (LD) cycle play in entraining the circadian timing system of primates, squirrel monkeys (Saimiri sciureus) were exposed to 24 hr LD cycles in which the light duration (photoperiod) was varied from 1 sec to 23 hr. The monkeys were maintained in isolation and the circadian rhythm of drinking was monitored. The photoperiod was first gradually shortened until constant darkness was reached. Even in extremely short photoperiods of only one second of light per day, the drinking rhythm remained synchronized to the 24 hr period of the LD cycle. In the second set of experiments, the photoperiod was gradually lengthened until constant light was achieved. The drinking rhythm of all monkeys was synchronized by 21 hr photoperiods (LD 21:3), but free-ran in 23 hr photoperiods (LD 23:1) which provided a 1 hr dark pulse each day. The tonic effects of light may contribute to the difference between the ability to entrain to short versus long photoperiods. In constant darkness the free-running period was close to 24 hr, thus reducing the phase-resetting necessary to achieve entrainment to a 24 hr period by short light pulses. However, in constant light or in the long photoperiods which did not entrain (LD 23:1) the free-running period of the drinking rhythm was greater than 25 hr, thus requiring a much larger daily phase shift to achieve entrainment to a 24 hr period.
Squirrel monkeys (Saimiri sciureus) demonstrate prominent circadian (approx 24 h) rhythms in many behavioral and physiological variables including drinking and body temperature. Both of these rhythms can be entrained by a 24-h light-dark cycle (LD 12:12) but will free-run with an endogenous period in a constantly illuminated (LL:600 lx) environment free of time cues. After radio-frequency lesions were placed stereotaxically in the suprachiasmatic nuclei (SCN) of five monkeys, the circadian rhythm of drinking behavior was disrupted when the monkeys were maintained in LL. However, the circadian rhythm in core body temperature in these animals persisted in LL with a significant circadian spectral component following destruction of the SCN. The SCN thus appear to be of fundamental importance for regulating the circadian organization of drinking; however, an oscillator located elsewhere in the squirrel monkey is capable of generating the core body temperature rhythm.
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Renal and hemocynamic responses to central vascular volume expansion induced by 4 hr of continuous lower body positive air pressure (LBPP) were examined in conscious, chair-restrained squirrel monkeys in a light/dark (12:12) cycle. LBPP (30 mmHg) during both day (1200--1600) and night (0000--0400) induced similar 4 cmH2O stable increases in central venous pressure (P < 0.001), rises in heart rate of 25 beat/min (P < 0.001), and small transient elevations in mean arterial blood pressure. In contrast, while daytime LBPP induced a significant increase in urine flow (V) from 2.12 +/- 0.31 to 3.5 +/- 0.42 ml/h (P < 0.05), and sodium excretion (UNaV) from 71.1 +/- 14 to 271.2 +/- 37 mueq/h (P < 0.001), there was a marked nocturnal inhibition of the response to LBPP, with no significant increases in V or UNaV. Urine osmolality decreased by more than 50% at both times of pressure exposure; potassium excretion was not significantly affected by either exposure and drinking was suppressed during daytine LBPP. Comparisons of the time course and diurnal regulation of the urinary responses suggest that several separate efferent control pathways are involved.
The characteristics and control of the circadian rhythms of core body temperature (colonic) and skin temperature (tail) were studied in chair-acclimatized squirrel monkeys (Saimiri sciureus). When animals were entrained to a light-dark cycle (12 h 600 lx; 12 h less than 1 lx) these two temperatures displayed prominent, reproducible, tightly coupled circadian rhythms. In contsant light of 600 lx, where no other effective circadian time cues were present, both temperature rhythms persisted with free-running periods. Within each animal, however, these rhythms were not as tightly coupled to one another as in LD. On occasion colonic and tail temperature rhythms free-ran with different circadian periods and some animals demonstrated "splitting" of the colonic temperature rhythm, with the colonic temperature rhythm displaying a bimodal pattern. These results suggest that the circadian rhythm of body temperature in primates is under the control of more than one potentially independent circadian oscillator.
Squirrel monkeys synchronized to a 24-hour light-dark cycle show a prominent circadian rhythm in body temperature which is regulated against mild environmental cold exposures throughout the 24-hour day. However, cold exposures produce significant decreases in core body temperature when the circadian rhythms of the animal are free-running in the absence of environmental time cues. Effective thermoregulation appears to require the precise internal synchronization of the circadian timekeeping system.
Several circadian rhythms in squirrel monkeys (Saimiri sciureus) entrained by two different agents were studied to compare their mode of coupling with the environmental zeitgebers. Synchronization was accomplished either by light-dark cycles consisting of 12 h of 600 lx followed by 12 h of less than 1 lx (LD 12:12), or by eat-fast cycles in which the animals could eat for 3 h and then had to fast for the remaining 21 h each day (EF 3:21). The rhythms of drinking, colonic temperature, and urinary potassium and water excretion were measured in chair-acclimatized monkeys. The drinking and urinary rhythms were more reproducible (smaller mean variance) and more stable (smaller standard deviation of the timing of a phase reference point) in EF than in LD cycles, whereas the temperature rhythm was more tightly controlled by LD cycles than by EF cycles. In constant light an 8-h phase delay in the EF cycle caused the drinking and urinary rhythms to resynchronize to the EF cycle within one day, while the temperature rhythm required about 6 days to resynchronize. In contrast, previously published data for a similar phase delay in the LD cycle with food available ad libitum show that the drinking and temperature rhythms resynchronized more rapidly than the urinary rhythms. These results indicate that separate mechanisms are involved in transducing temporal cues from LD and EF cycles in the circadian timekeeping system of these nonhuman primates.
The relative contributions of light-dark (LD) cycles and feeding (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-h LD cycles consisting of 12 h of 600 lx followed by 12 h of less than 1 ls and concurrent 24-h EF cycles in which the animals ate for 3 h and then fasted for 21 h. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-h LD cycles (LD 11.5:11.5) and 24-h EF cycles (EF 3:21). Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.
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Upon exposure of rats to 2 G environments (achieved by centrifugation), there occurred a rapid decrease in colonic temperature (Tco) followed, after about 50 min, by a slow recovery toward precentrifugation levels. The initial drop in Tco was accompanied by decreases in hypothalamic and spinal cord temperatures and increases in tail temperature (Tta). In contrast to this anomalous response (i.e., increased heat loss (manifested by increased Tta) despite decreasing temperature at spinal and hypothalamic thermoreceptor areas) the return toward normal Tco appeared to involve appropriate thermoregulatory responses. The initial fall in Tco was decreased in magnitude by inverting the rat during acceleration, thereby suggesting that mechanical forces acting on the brain may underlie this temperature decrease. Exposure to cold during centrifugation allowed further examination of the thermoregulatory system. Unlike the initial acceleration-induced changes, the cold-evoked fall in Tco was not accompanied by increasing Tta and was modified by the environmental conditioning of the rats. These results are consistent with the view that exposure to 2 G adversely affects the thermoregulatory ability of rats challenged by cold.