Tamae Yoda

Efferent projection from the preoptic area for the control of non-shivering thermogenesis in rats

1 To investigate the characteristics of efferent projections from the preoptic area for the control of non‐shivering thermogenesis, we tested the effects of thermal or chemical stimulation, and transections of the preoptic area on the activity of interscapular brown adipose tissue in cold‐acclimated and non‐acclimated anaesthetized rats. 2 Electrical stimulation of the ventromedial hypothalamic nucleus (VMH) elicited non‐shivering thermogenesis in the brown adipose tissue (BAT); warming the preoptic area to 41.5 °C completely suppressed the thermogenic response. 3 Injections of d,l‐homocysteic acid (DLH; 0.5 mm, 0.3 μl) into the preoptic area also significantly attenuated BAT thermogenesis, whereas injections of control vehicle had no effect. 4 Transections of the whole hypothalamus in the coronal plane at the level of the paraventricular nucleus induced rapid and large rises in BAT and rectal temperatures. This response was not blocked by pretreatment with indomethacin. The high rectal and BAT temperatures were sustained more than 1 h, till the end of the experiment. Bilateral knife cuts that included the medial forebrain bundle but not the paraventricular nuclei elicited similar rises in BAT and rectal temperatures. Medial knife cuts had no effect. 5 These results suggest that warm‐sensitive neurones in the preoptic area contribute a larger efferent signal for non‐shivering thermogenesis than do cold‐sensitive neurones, and that the preoptic area contributes a tonic inhibitory input to loci involved with non‐shivering thermogenesis. This efferent inhibitory signal passes via lateral, but not medial, hypothalamic pathways.

Autonomic and behavioural thermoregulation in starved rats

1 We investigated the mechanism of starvation‐induced hypothermia in rats. 2 Threshold core temperatures (Tcor) for tail skin vasodilatation and cold‐induced thermogenesis were determined after a 3 day starvation using a chronically implanted intravenous thermode. Food deprivation significantly lowered the threshold Tcor for heat production, but did not affect the heat loss threshold. 3 Thermogenic response to a fall in Tcor below its threshold was enhanced by starvation. 4 Preferred ambient temperatures (Tpref) and Tcor were measured before and during a 3 day starvation in a thermal gradient. The 3 day starvation significantly lowered Tcor only in the light phase of the day. The level of hypothermia was the same throughout the fasting period, while Tpref gradually increased during the 3 days of starvation. 5 When rats were starved at a constant ambient temperature of 25°C (no thermal gradient), their Tcor levels were comparable with those of the rats kept in the thermal gradient. 6 The results suggest that, in rats, hypothermia caused by starvation was not due to a decrement in thermogenic capability, but was due to a decrease in the threshold for the activation of thermogenesis.

Brain activation during whole body cooling in humans studied with functional magnetic resonance imaging

Regional activation of the brain was studied in humans using functional magnetic resonance imaging during whole body cooling that produced thermal comfort/discomfort. Eight normal male subjects lay in a sleeping bag through which air was blown, exposing subjects to cold air (8 degrees C) for 22 min. Each subject scored their degree of thermal comfort and discomfort every min. As the subjects reported more discomfort the blood oxygen level dependent response in the bilateral amygdala increased. There was no activation in the thalamus, somatosensory, cingulate, or insula cortices. This result suggests that the amygdala plays a role in the genesis of thermal discomfort due to cold.

Concepts to utilize in describing thermoregulation and neurophysiological evidence for how the system works

We would like to emphasize about the system involved with homeostatic maintenance of body temperature. First, the primary mission of the thermoregulatory system is to defend core temperature (Tcore) against changes in ambient temperature (Ta), the most frequently encountered disturbance for the system. Ta should be treated as a feedforward input to the system, which has not been adequately recognized by thermal physiologists. Second, homeostatic demands from outside the thermoregulatory system may require or produce an altered Tcore, such as fever (demand from the immune system). There are also conditions where some thermoregulatory effectors might be better not recruited due to demands from other homeostatic systems, such as during dehydration or fasting. Third, many experiments have supported the original assertion of Satinoff that multiple thermoregulatory effectors are controlled by different and relatively independent neuronal circuits. However, it would also be of value to be able to characterize strictly regulatory properties of the entire system by providing a clear definition for the level of regulation. Based on the assumption that Tcore is the regulated variable of the thermoregulatory system, regulated Tcore is defined as the Tcore that pertains within the range of normothermic Ta (Gordon in temperature and toxicology: an integrative, comparative, and environmental approach, CRC Press, Boca Raton, 2005), i.e., the Ta range in which an animal maintains a stable Tcore. The proposed approach would facilitate the categorization and evaluation of how normal biological alterations, physiological stressors, and pathological conditions modify temperature regulation. In any case, of overriding importance is to recognize the means by which an alteration in Tcore (and modification of associated effector activities) increases the overall viability of the organism.

Relative importance of different surface regions for thermal comfort in humans

In a previous study, we investigated the contribution of the surface of the face, chest, abdomen, and thigh to thermal comfort by applying local temperature stimulation during whole-body exposure to mild heat or cold. In hot conditions, humans prefer a cool face, and in cold they prefer a warm abdomen. In this study, we extended investigation of regional differences in thermal comfort to the neck, hand, soles, abdomen (Experiment 1), the upper and lower back, upper arm, and abdomen (Experiment 2). The methodology was similar to that used in the previous study. To compare the results of each experiment, we utilized the abdomen as the reference area in these experiments. Thermal comfort feelings were not particularly strong for the limbs and extremities, in spite of the fact that changes in skin temperature induced by local temperature stimulation of the limbs and extremities were always larger than changes that were induced in the more proximal body parts. For the trunk areas, a significant difference in thermal comfort was not observed among the abdomen, and upper and lower back. An exception involved local cooling during whole-body mild cold exposure, wherein the most dominant preference was for a warmer temperature of the abdomen. As for the neck and abdomen, clear differences were observed during local cooling, while no significant difference was observed during local warming. We combined the results for the current and the previous study, and characterized regional differences in thermal comfort and thermal preference for the whole-body surface.

Involvement of the suprachiasmatic nucleus in body temperature modulation by food deprivation in rats

Recently we found that food-deprived rats kept under a light-dark cycle showed a progressive reduction in body temperature during the light phase on each subsequent day while body temperature in the dark phase did not differ from baseline values. In this study, we investigated the effect of lesioning the hypothalamic suprachiasmatic nucleus (SCN) on body temperature modulation by food deprivation. In the SCN-lesioned rats in which daily rhythms of body temperature and activity were abolished, body temperature was unchanged by food deprivation. We also examined the effect of food deprivation on the daily changes in Fos expression in the SCN. Under normal fed conditions the number of SCN cells expressing Fos is high during the day and low at night. Food deprivation attenuated the amplitude of this daily change in Fos expression in the SCN. This tendency was prominent in the dorsal part of the SCN, while the ventral part showed no effect of food deprivation. These findings suggest that the SCN plays some role in body temperature modulation due to food deprivation.

New apparatus for studying behavioral thermoregulation in rats

The operant system described here contains a box that can be convectively heated or cooled. A rat moves freely in the box. Its location is monitored photoelectrically while its deep body temperature is monitored by a telemetry system. In heat-escape experiments, hot air (40 degrees C) flows through the box. When the rat enters a reward zone the air source is switched and cold air (0 degrees C) flows through the box for a given period (30 s). Conversely, in cold-escape experiments cold air flows through the box and when the rat enters the reward zone the air source is switched to a warm one. Experiments show that rats quickly learn to stay near the reward zone and move in and out of it periodically. This system is based on behavior more natural than the frequently used lever-pressing response, and has many advantages for use in studies involving behavioral thermoregulation.

Effects of alcohol on autonomic responses and thermal sensation during cold exposure in humans

We investigated the effects of alcohol on thermoregulatory responses and thermal sensations during cold exposure in humans. Eight healthy men (mean age 22.3+/-0.7 year) participated in this study. Experiments were conducted twice for each subject at a room temperature of 18 degrees C. After a 30-min resting period, the subject drank either 15% alcohol at a dose of 0.36 g/kg body weight (alcohol session) or an equal volume of distilled water (control session), and remained in a sitting position for another 60 min. Mean skin temperature continued to decrease and was similar in control and alcohol sessions. Metabolic rate was lower in the alcohol session, but the difference did not affect core temperature, which decreased in a similar manner in both alcohol and control sessions (from 36.9+/-0.1 degrees C to 36.6+/-0.1 degrees C). Whole body sensations of cold and thermal discomfort became successively stronger in the control session, whereas these sensations were both greatly diminished after drinking alcohol. In a previous study we performed in the heat, using a similar protocol, alcohol produced a definite, coordinated effect on all autonomic and sentient heat loss effectors. In the current study in the cold, as compared to responses in the heat, alcohol intake was followed by lesser alterations in autonomic effector responses, but increased changes in sensations of temperature and thermal discomfort. Overall, our results indicate that although alcohol influences thermoregulation in the cold as well as in the heat, detailed aspects of the influence are quite different.

Estimation of the core temperature control during ambient temperature changes and the influence of circadian rhythm and metabolic conditions in mice.

It has been speculated that the control of core temperature is modulated by physiological demands. We could not prove the modulation because we did not have a good method to evaluate the control. In the present study, the control of core temperature in mice was assessed by exposing them to various ambient temperatures (Ta), and the influence of circadian rhythm and feeding condition was evaluated. Male ICR mice (n=20) were placed in a box where Ta was increased or decreased from 27°C to 40°C or to -4°C (0.15°C/min) at 0800 and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature (Tcore) was monitored by telemetry. The relationship between Tcore and Ta was assessed. The range of Ta where Tcore was relatively stable (range of normothermia, RNT) and Tcore corresponding to the RNT median (regulated Tcore) were estimated by model analysis. In fed mice, the regression slope within the RNT was smaller in the nighttime than in the daytime (0.02 and 0.06, respectively), and the regulated Tcore was higher in the nighttime than in the daytime (37.5°C and 36.0°C, respectively). In the fasted mice, the slope remained unchanged, and the regulated Tcore decreased in the nighttime (0.05 and 35.9°C, respectively), while the slopes in the daytime became greater (0.13). Without the estimating individual thermoregulatory response such as metabolic heat production and skin vasodilation, the analysis of the Ta-Tcore relationship could describe the character of the core temperature control. The present results show that the character of the system changes depending on time of day and feeding conditions.

The regional difference in temperature related sensations

It is unclear how our brain predicts reward and punishing outcome on perception of ambiguous stimuli in environment. To investigate relationship between perceptually ambiguous stimuli and reward processing on them, we examined reward-predicting brain activity on high and low coherency random dot motion stimuli by using fMRI. First, we trained subjects to establish a contingency between particular direction of motion stimuli and delivery of reward. Then, we presented high and low coherence motion stimuli, and asked subjects to judge direction of the motion. Juice or saliva was followed by stimulus direction associated with reward or neutral outcome, respectively. The data at the time of cue presentation showed that activation in the caudate was correlated with reward prediction based on stimulus direction that was influenced by coherence level, whereas reward-predicting activation based on subject’s performance was observed in the putamen. The results suggested that stimulus-based and perception-based reward prediction could be dissociated in the basal ganglia.