6.2 The hypothalamus as central regulator
Research in the past 30–40 years has established that the hypothalamus, which lies below the thalamus and above the optic nerve chiasma and the pituitary gland in the brain, fulfils all of the functions listed above, at least in part. The main function of the hypothalamus is homeostasis. Factors such as blood pressure, body temperature, fluid and electrolyte balance, and body weight are held to constant values called the set-points. Although set-points can vary over time, from day to day they are remarkably fixed.
The hypothalamus is an internal regulator of biorhythms. The supraoptic nucleus (SON) is found just above the optic tract in both brain hemispheres (Figure 35). It is the site of the ‘clock’ in mammals that sets an internal daily (circadian) and annual rhythm by which body functions such as metabolism, core body temperature, reproductive physiology and locomotive behaviour are governed. The endogenous rhythms of SON nerve cells are entrained to environmental cues such as daylength with reference to sensory signals from peripheral sense organs, particularly the eyes and light-sensitive receptors within the brain itself. The onset of torpor and hibernation seem to occur in golden hamsters (Mesocricetus auratus) during the active phase of the circadian cycle, but hamsters of the same species but with genotypes causing longer or shorter natural circadian rhythms did not experience different bout-lengths of torpor. Thus the hypothalamic oscillator relinquishes control over the timing of hibernation bouts once they have started. It seems likely that during hibernation, the ventromedial hypothalamus, close to the midline of the brain, becomes more important in thermoregulation.
Figure 35a shows an experiment with a marmot (Marmota flaviventris) in its euthermic phase, in which whole-body metabolic rate is measured using a calorimeter, whilst the temperature of the hypothalamus, T hy, is being both adjusted and monitored in the conscious animal using a water-filled catheter and a thermocouple. When T hy is lowered below 36.5° C, metabolic rate increases with an intensity proportional to the difference between T hy and the threshold temperature. Figure 35b is the response in another individual, which is in hibernation at a T a of 5° C.
What do you deduce from Figure 35b?
The shape of the curve is identical to that in Figure 35a, suggesting that metabolic rate changes at a threshold temperature during hibernation as well. However, there are two striking differences. First, the threshold temperature in the hibernating marmot is about 7° C, compared with 36.5° C in the euthermic marmot. Secondly, the metabolic rate is much lower (10% of that in the euthermic marmot) though the response to lowered T hy (a fourfold increase) is about the same. These experiments show that the hypothalamus is a thermosensitive centre which is linked to effector systems that raise the metabolic rate (and produce heat). The temperature set-point has been lowered from the normal level of 37° C in the hibernating animal but the proportional metabolic response to lowering the temperature below the threshold is the same in euthermic and hibernating animals.
In the dormouse (Muscardinus avellanarius), which hibernates on its back with hind legs exposed, it is possible to cool the feet in the same way using double-layered, jacketed half-boots in which a temperature-controlled liquid can be pumped between the two layers of the boot. With this device, the temperature of the hind feet could be altered without affecting deep-body or brain temperature. It was found that, irrespective of T hy, cooling the hind feet stimulated an increase in the metabolic heat response. This observation implies that the mechanism governing the set-point may not always reside in the pre-optic area of the anterior hypothalamus (POAH). Recent studies in rats, in which BAT thermogenesis was measured in response to direct electrical stimulation of the central nervous system (CNS), suggest that there are groups of nerve cells forming thermoregulatory centres at many sites in the brain and spinal cord.
How is the progressive reduction of temperature accomplished during entry into hibernation? It might be that the set-point remains in operation, but that its value is steadily shifted downwards. The following experiments, performed by Florant and Heller (1977), explore these possibilities. By manipulating T hy of marmots (Marmota flaviventris) entering a bout of torpor, he was able to determine absolute values for the T hy threshold (T set), and see how these indices changed with time. Figure 36 shows such an experiment in two individuals. T hy is varied, using a catheter arrangement and Ts (the skin temperature) is measured. The metabolic response is indicated on the lower traces. The marmot in Figure 36a is entering hibernation fairly smoothly, whereas, as judged by the frequent bursts of high metabolic rate (see arrows), the marmot in Figure 36b is progressing into hibernation rather irregularly. The cream and blue bands on each figure indicate the periods during which T hy was being manipulated (lowered (cream) and raised (blue), respectively). Take the left-hand trace (a) first. Depressing T hy in the early stages stimulates an increase in metabolic response, but 30 minutes later, the same decrease in T hy has no effect on metabolic rate. This experiment suggests that the threshold temperature has fallen from 22–27° C to 23–24° C in 30 minutes. At 3 hours into hibernation, lowering the Thy even below 23° C has little effect initially on metabolic rate. In the right-hand trace (b), Ts also declines with time but is consistently above the manipulated T hy, as indicated by the bursts of metabolic activity. Therefore, at any one time, the threshold may be above or below the actual T hy. If the threshold is above it, the entrance is irregular, interrupted by bursts of metabolic heat production which slow the fall in T b. Florant and Heller concluded that the rate of entry into hibernation is limited by the rate at which threshold T hy falls. It seems, therefore, that entrance into hibernation and the lowering of T b are controlled events. Using experimental data such as those gained from Figure 36, it is possible to plot the declining threshold temperature. Figure 37 (Heller et al., 1977) shows such a plot for a golden-mantled ground squirrel entering hibernation. The filled circles represent actual hypothalamic temperatures at specific times during entry. Manipulation of T hy reveals that the threshold for metabolic heat production is somewhere in the range indicated by the vertical line below each dot. This process of continuously varying the controlled level of a feedback system has been called rheostasis, to distinguish it from homeostasis, which has implications of a fixed set-point.
The model exemplified by the ground squirrel entering hibernation may not, however, represent a universal phenomenon. In the eastern chipmunk (Tamias striatus), a facultative hibernator, a gradual, controlled decline in Ts on entering hibernation is often absent. Manipulating the hypothalamic temperature may have no effect in chipmunks hibernating with a T b of about 4° C, until about 2.1° C is reached (which is T alarm for this animal), when there is full arousal (Figure 38) (Wang and Hudson, 1971). Thus, the animal has the ability to increase thermogenesis when cold as a result of T hy falling too low, but does not normally control and defend Th above the T alarm level – at least not as a result of changes in hypothalamic temperature.