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A global bioheat model with self-tuning optimal regulation of body temperature using Hebbian feedback covariance learning.

In the lower brain, body temperature is continually being regulated almost flawlessly despite huge fluctuations in ambient and physiological conditions that constantly threaten the well-being of the body. The underlying control problem defining thermal homeostasis is one of great enormity: Many systems and sub-systems are involved in temperature regulation and physiological processes are intrinsically complex and intertwined. Thus the defining control system has to take into account the complications of nonlinearities, system uncertainties, delayed feedback loops as well as internal and external disturbances. In this paper, we propose a self-tuning adaptive thermal controller based upon Hebbian feedback covariance learning where the system is to be regulated continually to best suit its environment. This hypothesis is supported in part by postulations of the presence of adaptive optimization behavior in biological systems of certain organisms which face limited resources vital for survival. We demonstrate the use of Hebbian feedback covariance learning as a possible self-adaptive controller in body temperature regulation. The model postulates an important role of Hebbian covariance adaptation as a means of reinforcement learning in the thermal controller. The passive system is based on a simplified 2-node core and shell representation of the body, where global responses are captured. Model predictions are consistent with observed thermoregulatory responses to conditions of exercise and rest, and heat and cold stress. An important implication of the model is that optimal physiological behaviors arising from self-tuning adaptive regulation in the thermal controller may be responsible for the departure from homeostasis in abnormal states, e.g., fever. This was previously unexplained using the conventional "set-point" control theory.

Adaptation, Physiological↗

Gravity and thermoregulation: metabolic changes and circadian rhythms.

Gravity appears to alter thermoregulation through changes in both the regulated level of body temperature and the rhythmic organization of temperature regulation. Gravity has been hypothesized to have an associated metabolic cost. Increased resting energy expenditure and dietary intake have been observed in animals during centrifuge experiments at hypergravity. Thus far, only animals have shown a corresponding reduction in metabolism in microgravity. Altered heat loss has been proposed as a response to altered gravitational environments, but remains documented only as changes in skin temperature. Changes in circadian timing, including the body temperature rhythm, have been shown in both hypergravity and microgravity, and probably contribute to alterations in sleep and performance. Changes in body temperature regulation may result from circadian disturbance, from the direct or indirect actions of gravity on the regulated temperature, or from changes in thermoregulatory effectors (heat production and heat loss) due to altered gravitational load and convective changes. To date, however, we have little data on the underlying thermoregulatory changes in altered gravity, and thus the precise mechanisms by which gravity alters temperature regulation remain largely unknown.

Animals↗

Thiamine deficiency-induced disruptions in the diurnal rhythm and regulation of body temperature in the rat.

In the present study, diurnal rhythm and regulation of body temperature were monitored during and several weeks following pyrithiamine-induced thiamine deficiency (PTD group, n=8) or pairfeeding (control group, n=9). A significant decline of core body temperature and a disruption of its diurnal rhythm were observed at varying stages of PTD treatment. Following thiamine administration and return to thiamine-fortified chow, body temperature continued to fall and several days transpired before body temperature and its diurnal rhythm were returned to normal. When exposed to warm and cold environments, no significant group differences were observed in either the maximum temperature change or the time elapsed to reach maximal temperature change. Histological examination revealed necrotic lesions in thalamus and mammillary body in the PTD group characteristic of Wernicke's encephalopathy. No significant damage was observed in the medial preoptic and suprachiasmatic nuclei, brain regions involved in the regulation of body temperature and circadian rhythm. These findings suggest that hypothermia and disruption of the diurnal rhythm of body temperature can be reversed by restoration of adequate thiamine levels and are related to biochemical and physiological disturbances rather than gross structural changes.

Animals↗

Physiological and cellular adaptations of zebu cattle to thermal stress.

During their separate evolution from Bos taurus, zebu cattle (Bos indicus) have acquired genes that confer thermotolerance at the physiological and cellular levels. Cattle from zebu breeds are better able to regulate body temperature in response to heat stress than are cattle from a variety of B. taurus breeds of European origin. Moreover, exposure to elevated temperature has less deleterious effects on cells from zebu cattle than on cells from European breeds. Superior ability for regulation of body temperature during heat stress is the result of lower metabolic rates as well as increased capacity for heat loss. As compared to European breeds, tissue resistance to heat flow from the body core to the skin is lower for zebu cattle while sweat glands are larger. Properties of the hair coat in zebu cattle enhance conductive and convective heat loss and reduce absorption of solar radiation. At the cellular level, genetic adaptations to resist deleterious effects of elevated temperature result in preimplantation embryos from zebu being less likely to be inhibited in development by elevated temperature than are embryos from European breeds. The zebu genotype has been utilized in crossbreeding systems to develop cattle for beef and dairy production systems in hot climates but success has been limited by other unfavorable genetic characteristics of these cattle. An alternative scheme is to incorporate specific thermotolerance genes from zebu cattle into European breeds while avoiding undesirable genes. Once specific genes responsible for thermotolerance in zebu have been identified or mapped, breeding strategies such as marker-assisted selection and transgenics can be applied to further the exploitation of the zebu genotype for cattle production systems.

Animals↗

Thermal quality influences effectiveness of thermoregulation, habitat use, and behaviour in milk snakes.

We investigated the link between thermal quality and the effectiveness of thermoregulation in milk snakes in a thermally challenging environment. We defined thermoregulatory effectiveness as the extent to which an individual maintains its body temperature (Tb) closer to the preferred range (Tset) than allowed by the thermal quality of its environment. We defined thermal quality as the magnitude of the difference between operative environmental temperatures (Te) and Tset. Because ectotherms regulate body temperatures through choice of habitat and behavioural adjustments, we also examined the link between thermoregulation, habitat use and behaviour. During 2003-2004, we located 25 individuals 890 times, and recorded their Tb. Thermal quality was lower in the spring and fall than in the summer, and was lower in forests than in open habitats. Milk snakes thermoregulated more effectively in the spring than in the summer and fall, and more effectively in the forest than in open habitats. Milk snakes had a strong preference for open habitats in all seasons, which was likely to facilitate behavioural thermoregulation. The preference for open habitats was equally strong in all seasons and, therefore, the higher effectiveness of thermoregulation was not a result of altered habitat use. Instead, milk snakes modified their behaviour and were seen basking more and moved less in the spring than in the summer.

Animals↗

Regulation of body temperature in postmenopausal women: interactions between bromocriptine and the endogenous opioid system.

The role exerted by the endogenous opioid system on thermoregulation has been studied in nine postmenopausal women before and after the chronic administration of the dopamine agonist bromocriptine (5 mg/day). These women randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, before and after 30 days of bromocriptine administration. Body temperature as evaluated by rectal temperature, did not vary during saline infusion performed both before and after 30 days of bromocriptine administration. In untreated women naloxone infusion significantly reduced body core temperature. The hypothermic response to naloxone was significantly greater following chronic bromocriptine administration. These results indicate that bromocriptine seems to increase the activity of the endogenous opioid system on the mechanisms which regulate body temperature in postmenopausal women.

Body Temperature Regulation↗

The energetics of New Zealand's ducks.

Measurements on rates of metabolism and temperature regulation are presented from nine populations of seven species of ducks resident in New Zealand. An analysis of these data and those from 18 additional species obtained from the literature indicates that basal rate of metabolism in anatids correlates with body mass and restriction to the Australian-New Zealand region: these 'southern' species have basal rates that average 70% of those from the Northern Hemisphere. The low basal rates of southern anatids may reflect reduced pectoral muscle masses in association with the absence of migratory habits and/or life on land masses without eutherian predators. New Zealand flightless teal (Anas aucklandica nesiotis, Anas aucklandica aucklandica) do not have mass-independent basal rates that differ from those found in flighted ducks living in the same region, although flightless teal have lower total basal rates than most ducks as a result of small masses. Minimal thermal conductance in this sample is determined by body mass alone. Regulated body temperature is negatively correlated with body mass.

Animals↗

Changes of body temperature and thermoregulatory responses of freely moving rats during GABAergic pharmacological stimulation to the preoptic area and anterior hypothalamus in several ambient temperatures.

Action of gamma-aminobutyric acid (GABA) in the preoptic area and anterior hypothalamus (PO/AH) has been implicated to regulate body temperature (T(b)). However, its precise role in thermoregulation remains unclear. Moreover, little is known about its release pattern in the PO/AH during active thermoregulation. Using microdialysis and telemetry techniques, we measured several parameters related to thermoregulation of freely moving rats during pharmacological stimulation of GABA in normal (23 degrees C), cold (5 degrees C), and hot (35 degrees C) ambient temperatures. We also measured extracellular GABA levels in the PO/AH during cold (5 degrees C) and heat (35 degrees C) exposure combined with microdialysis and high performance liquid chromatography (HPLC). Perfusion of GABA(A) agonist muscimol into the PO/AH increased T(b), which is associated with increased heart rate (HR), as an index of heat production in all ambient temperatures. Although tail skin temperature (T(tail)) as an index of heat loss increased only under normal ambient temperatures, its response was relatively delayed in comparison with HR and T(b), suggesting that the increase in T(tail) was a secondary response to increased HR and T(b). Locomotor activity also increased in all ambient temperatures, but its response was not extraordinary. Interestingly, thermoregulatory responses were different after perfusion of GABA(A) antagonist bicuculline at each ambient temperature. In normal ambient temperature conditions, perfusion of bicuculline had no effect on any parameter. However, under cold ambient temperature, the procedure induced significant hypothermia concomitant with a decrease in HR in spite of hyperactivity and increase of T(tail). It induced hyperthermia with the increase of HR but no additional change of T(tail) in hot ambient temperature conditions. Furthermore, the extracellular GABA level increased significantly during cold exposure. Its release was lower during heat exposure than in a normal environment. These results indicate that GABA in the PO/AH is an important neurotransmitter for disinhibition of heat production and inhibition of heat loss under cold ambient temperature. It is a neurotransmitter for inhibition of heat production under hot ambient temperature.

Analysis of Variance↗

Acid-base regulation during thermal panting in the fowl (Gallus domesticus): comparison between breeds.

1. The effects of high ambient temperatures on blood acid base status were studied in four breeds of fowl. 2. All breeds efficiently regulated body temperature below ambient temperature at 45 degrees C (Tb = 38.521 + 0.110Ta, at 25-45 degrees C). 3. A slight hypocapnia was partly compensated for by a decreased HCO3 concentration. This resulted in only a slight respiratory alkalosis at extreme temperatures (+0.021 and +0.042 pH units at 42 and 45 degrees C, respectively). 4. Changes in Paco2 were negatively correlated with tidal volume: Paco2 (torr) = 33.10390 - 1.17493 VT(ml); r = -0.925, P much less than 0.001. 5. The present findings are consistent with an hypothesis that modulation of tidal volume during thermal panting might play a major role in acid-base regulation.

Acid-Base Equilibrium↗

Opposite regulation of body temperature by cholinergic input to the paraventricular nucleus and supraoptic nucleus in rats.

Hypothalamic cholinergic system plays an important role in the regulation of body temperature and fluid balance. We have previously shown that cholinergic stimulation of the anterior hypothalamus and preoptic area was accompanied by a fall in body temperature, increased water intake, and increased Fos protein in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In the present study, to estimate the role played by cholinergic input to the PVN and SON in thermoregulation and water intake, we used microdialysis for cholinergic stimulation with neostigmine and analysis of the nucleus, and also investigated immunoreactivity for c-Fos protein in the brain. This stimulation increased extracellular concentration of acetylcholine in these nuclei. Stimulation of the PVN decreased body temperature and increased water intake. On the other hand, stimulation of the SON increased body temperature. Both in PVN-stimulated and SON-stimulated rats, c-Fos-like immunoreactivity (Fos-IR) was evident in the PVN, SON and certain regions including locus coeruleus (LC), area postrema and nucleus of the solitary tract (NTS). Addition of atropine to the dialysis medium attenuated the increase of Fos-IR and suppressed the cholinergic stimulation-induced responses in body temperature and water intake. These results suggest that cholinergic muscarinic mechanisms in PVN and SON play an opposite function in the regulation of body temperature. The same neuronal pathway including LC and NTS may participate in an advance both in hypothermia and in hyperthermia.

Acetylcholine↗

Incubation temperature modulates post-hatching thermoregulatory behavior in the Madagascar ground gecko, Paroedura pictus.

All vertebrates regulate body temperature within narrow limits, regardless of their physiological capabilities. When do these limits develop, and can they be modified by manipulations of the developmental thermal environment? We addressed these questions by incubating the eggs of the Madagascar ground gecko, Paroedura pictus, at three temperatures and by assessing thermoregulatory behavior in hatchlings. Thermoregulatory behavior was assessed using a two-choice shuttle paradigm, and skin temperatures were measured non-invasively using infrared thermography. The shuttling behavior of hatchlings was systematically affected by the temperature at which they were incubated, and follow-up tests suggested that this effect persisted for at least three weeks post-hatching. The body temperature data from the shuttling experiment were used to model thermoregulatory behavior in a complex thermal environment; the model predicted systematic effects of incubation temperature on thermal preference. The specificity of the alteration in thermoregulatory behavior by incubation temperature is compelling and provides evidence for powerful pre-hatching influences on a fundamental, life-sustaining behavioral process.

Aging↗

Fever's glass ceiling.

The importance of an upper limit of the febrile response has been recognized since the time of Hippocrates. Although the precise temperature defining this limit varies according to the site at which body temperature is measured, human core temperature is almost never permitted to rise above 41 degrees C-42 degrees C during fever. There are compelling physiological reasons for such an upper limit of regulated body temperature. The mechanisms by which the limit is maintained are most likely complex and involve special properties of thermoregulatory neurons themselves, circulating endogenous antipyretics (such as arginine vasopressin and alpha-melanocyte-stimulating hormone), and soluble receptors for the (pyrogenic) cytokine mediators of the febrile response.

Animals↗

Environmental light and suprachiasmatic nucleus interact in the regulation of body temperature.

The mammalian biological clock, located in the suprachiasmatic nucleus (SCN), is crucial for circadian rhythms in physiology and behavior. However, equivocal findings have been reported on its role in the circadian regulation of body temperature. The goal of the present studies was to investigate the interaction between the SCN and environmental light in the regulation of body temperature. All recordings were performed by telemetry in free moving male Wistar rats. Firstly, we demonstrated an endogenous circadian rhythm in body temperature independent of locomotor activity. This rhythm was abolished by stereotactic lesioning of the SCN. Secondly, we demonstrated a circadian phase-dependent suppressive effect of light ('negative masking') on body temperature. Light suppressed body temperature more at the end of the subjective night (circadian time [CT] 22) than in the middle (CT 6) and at the end (CT 10) of the subjective day. This circadian-phase dependent suppression was not demonstrated in SCN-lesioned animals. Surprisingly, after half a year of recovery from lesioning of the SCN, light regained its suppressing action on body temperature, resulting in a daily body temperature rhythm only under light-dark conditions. In contrast to body temperature, light could not substantially mimic a daytime inhibitory SCN-output in the regulation of heart rate and locomotor activity. The present results suggest that, after lesioning of the SCN as main relay station for the immediate body temperature-inhibition by light, secondary relay nuclei can fully take over this function of the SCN. These findings provide a possible explanation for the controversy in literature over the question whether the SCN is required for the diurnal rhythm in body temperature. Furthermore, they show that light may have an acute effect on behavior and physiology of the organism via the SCN, which extends beyond the generally acknowledged effect on melatonin secretion.

Analysis of Variance↗

Effects of one- and two-stage lesions of the posterior hypothalamus on temperature regulation in the rat.

Rats received 1-stage bilateral and sequential unilateral (serial) lesions of the posterior hypothalamus and were tested for the ability to regulate body temperature after a lengthy recovery period. The groups with lesion differed from the sham-operated groups in the cold, although not under ambient or warm conditions. The fact that the serial lesion group performed the same as the 1-stage lesion groups in the cold is significant because earlier tests on these same animals revealed much better recovery after serial lesions in swimming, and a partial serial lesion effect in open field performance.

Animals↗

Temperature regulation in mice during withdrawal from ethanol dependence.

Temperature regulation during withdrawal from ethanol dependence was studied in mice. Dependence was induced utilizing ethanol vapor inhalation combined with injections of pyrazole, an alcohol dehydrogenase inhibitor. One control group received vehicle (0.9% NaCl); another received pyrazole (68.1 mg/kg) in vehicle. During withdrawal, mice were placed in a thermal gradient, with core temperature (Tc) and preferred temperature (Tpref) continuously recorded for 26 h. During the period of maximal withdrawal severity (4-10 h after removal from ethanol vapor), the withdrawal group was more active than controls. Withdrawal group Tc [36.4 +/- 0.1 (SE) degrees C] was similar to that of NaCl (36.2 +/- 0.1 degrees C) and pyrazole (36.3 +/- 0.2 degrees C) controls. Withdrawal group Tpref (30.5 +/- 0.5 degrees C) was significantly lower than either NaCl (33.5 +/- 0.3 degrees C) or pyrazole (32.9 +/- 0.5 degrees C) controls. Analysis of covariance with activity as covariate indicated that the difference between Tc and Tpref was greater for the withdrawal group and was due to more than increased activity. Mice withdrawing at constant temperature (29.5 degrees C) did not show Tc different from that of controls. These results support the conclusion that regulated body temperature is not altered during withdrawal. We propose that the lower Tpref of withdrawing mice represents a means of dissipating excess heat that is partly generated by the hypermetabolic state accompanying withdrawal from ethanol dependence.

Alcoholism↗

Operant control of convective cooling and microwave irradiation by the squirrel monkey.

Adult male squirrel monkeys (Saimiri sciureus) were individually chair-restrained in an air-conditioned Styrofoam box in the far field of a horn antenna. Each monkey first received extensive training to regulate the temperature of the air circulating through the box by selecting between 10 and 50 degrees C air source temperatures. Then, to investigate the ability of the animals to utilize microwaves as a source of thermalizing energy, 2450-MHz continuous wave microwaves accompanied by thermoneutral (30 degrees C) air were substituted for the 50 degrees C air. Irradiation at each of three power densities was made available, ie, at 20, 25, and 30 mW/cm2 [SAR = 0.15 (W/kg)/(mW/cm2)]. The percentage of time that the monkeys selected microwave irradiation paired with thermoneutral air averaged 90% at 20 and at 25 mW/cm2. The mean percentage declined reliably (p less than 0.001) to 81% at 30 mW/cm2, confirming the monkey's ability to utilize microwave irradiation as a source of thermal energy during the course of behavioral thermoregulation. All animals readily made the warm-air to microwave-field transition, regulating rectal temperature with precision by sequentially selecting 10 degrees C air, then microwave irradiation accompanied by 30 degrees C air. Although the selection of cooler air resulted in a slight reduction of skin temperatures, normal rectal temperature was maintained. The results indicate that the squirrel monkey can utilize a microwave source in conjunction with convective cooling to regulate body temperature behaviorally.

Air Conditioning↗