Contributions to Thermal Physiology: Satellite Symposium of the 28th International Congress of Physiological Sciences, Pécs, Hungary, 1980

Physiology

Central nervous control of body temperature

FUNCTIONAL ANATOMY OF THE HYPOTHALAMUS FROM THE POINT OF VIEW OF TEMPERATURE REGULATION

CLARK M. BLATTEIS,     Department of Physiology and Biophysics, University of Tennessee Center for the Health Sciences, Memphis, Tennessee 38163, USA

Publisher Summary

This chapter discusses the functional anatomy of the hypothalamus from the point of view of temperature regulation. The ability of the hypothalamus to trigger the total pattern of autonomic thermoregulatory responses has been repeatedly shown. The locus of greatest control appears to reside in the PO/AH. Animals with PO/AH lesions or topical anesthesia cannot maintain their body temperatures in cold or warm environments; locally cooling or heating this area causes appropriate autonomic thermoregulatory responses. Both warm- and cool-sensitive neurons have been identified; however, the cool-sensitive neurons may be interneurons receiving inhibitory inputs from nearby warm-sensitive neurons. PO/AH thermosensitive units receive afferent inputs from cutaneous thermoreceptors and from thermosensitive neurons in the spinal cord and the midbrain. The temperature controller function has been ascribed to these temperature-sensitive neurons or, alternatively, to adjacent, temperature-insensitive neurons. Putative neurotransmitters injected directly into the PO/AH induce either increases or decreases of body temperature, depending upon the species and other conditions. Temperature-sensitive units occur in the posterior hypothalamus, but they are few. Thermal stimulation or local injection of neurotransmitters may or may not evoke autonomic thermoeffector responses.

Endotherms utilize both autonomic and behavioral means of effector response to maintain body temperature. Both response modes are activated by peripheral and/or central temperature inputs; moreover, the operating characteristics of their controller(s) are similar. However, it is not yet clear whether these two systems are controlled by the same or different neural structures and circuits. A functional and, possibly, a spatial separation of the CNS controllers of the two response modes has been hypothesized. Individual components of autonomic and behavioral thermoregulation also may be controlled separately. This paper reviews the current knowledge in this area from the perspective of functional anatomy.

Autonomic Temperature Regulation

Hypothalamic control mechanisms.

Preoptic/anterior hypothalamus (PO/AH).

The ability of the hypothalamus to trigger the total pattern of autonomic thermoregulatory responses has been repeatedly shown. The locus of greatest control appears to reside in the PO/AH. Animals with PO/AH lesions or topical anesthesia cannot maintain their body temperatures in cold or warm environments; locally cooling or heating this area causes appropriate autonomic thermoregulatory responses (reviewed by Satinoff, 1974). Both warm- (Nakayama et al., 1963) and cool- (Hardy et al., 1964) sensitive neurons have been identified; however, the cool-sensitive neurons may be interneurons receiving inhibitory inputs from nearby warm-sensitive neurons (Boulant and Hardy, 1974). PO/AH thermosensitive units receive afferent inputs from cutaneous thermoreceptors (Hellon, 1970; Wit and Wang, 1968), and from thermosensitive neurons in the spinal cord (Guieu and Hardy, 1970) and the midbrain (Eisenman, 1974). Temperature controller function has been ascribed to these temperature-sensitive neurons (Boulant and Gonzalez, 1977); or, alternatively, to adjacent, temperature-insensitive neurons (reviewed by Hammel, 1968). Putative neurotransmitters injected directly into the PO/AH induce either increases or decreases of body temperature, depending upon the species and other conditions (reviewed by Bligh, 1979). It is uncertain, however, whether these transmitters act on the thermosensitive or other neurons (Jell, 1974). Zeisberger and Brück (1971) have localized an area immediately posterior to the thermosensitive neurons in the PO/AH which is norepinephrine-sensitive and activates heat production. They postulated that these cells generate the reference signal for the temperature regulation system.

Posterior hypothalamus (PH).

Temperature-sensitive units occur in the PH, but they are few (Edinger and Eisenman, 1970; Wünnenberg and Hardy, 1972). Thermal stimulation or local injection of neurotransmitters may or may not evoke autonomic thermoeffector responses (Adair, 1974; Lipton, 1973); local anesthesia does not affect autonomic thermoregulation (Humphreys et al., 1976). Hence, the PH may not be a controller for this system. On the other hand, this structure is a major site of convergence of temperature inputs (Nutik, 1973), and may be the origin of the central effector signal (Hardy, 1973). Puschmann and Jessen (1978) found in the PH of goats thermosensitive neurons which elicited thermoeffector responses inverse to those expected. They suggested that these units were nonspecific, and may be integrative structures which transduce incoming thermal signals into thermoeffector responses. Similar non-corrective autonomic responses to hypothalamic thermal stimulation have been found in penguins, and also ascribed to nonspecific temperature effects on hypothalamic integrative functions (Simon et al., 1976). The PH also may be providing an ionic reference input to the PO/AH temperature controller (Myers and Veale, 1970). It is generally agreed that the PH contains neurons which mediate shivering (reviewed by Hemingway, 1963).

Extrahypothalamic control mechanisms.

Midbrain.

The PO/AH, however, may not solely command the full pattern of defenses against thermal stress, because a variable capability for autonomic thermoregulation survives its destruction. Thus, when the midbrain reticular formation (MRF) is completely separated from the hypothalamus, thermoregulation in the cold is lost, but autonomic responses to heat persist (Andersson et al., 1965; Keller, 1963; Bard et al., 1970); however, these are raised to a higher threshold. But, if any tissue remains between the MRF and the hypothalamus, various components of the autonomic responses to heat or cold are evocable (Keller, 1938; Bard et al., 1970). Both warm- (Cabanac and Hardy, 1969) and cool- (Nakayama and Hardy, 1969) sensitive neurons have been identified in the MRF. Thermal stimulation evokes appropriate thermoeffector responses in some species (Cronin and Baker, 1977), but not in others (Adair and Stitt, 1971). Thus, the MRF may have some capacity for independent autonomic thermoregulation, but not in all species. Since the activating stimulus must be increased when its hypothalamic connections are severed, it may be that it usually is tonically inhibited by the PO/AH. Alternatively, since the MRF, and the serotonergic raphe cells it contains, may lie in the pathway through which thermal afferents ascend to the PO/AH (Dickenson, 1977; Eisenman, 1974), and in view of the possible involvement of serotonin in temperature regulation, separation of this area from its connections above could result in reduced responsiveness.

Pons and medulla.

A relative independence of thermoregulatory function also exists in pontine and low mesencephalic cats. Thus, when the transection is complete, lack of autonomic defenses against cold and persistence of heat loss responses appearing only at very high body temperatures are noted (Keller, 1963; Bard et al., 1970). However, when the transection spares either lateral or medial pathways, shivering is not impaired in the cold (Keller, 1938); and when the medial pons is ablated but the lateral pons spared, shivering appears even at room temperature (Connor and Crawford, 1969). These latter results have been interpreted as indicating that the shivering pathways (which pass laterally in the pons [Hemingway, 1963]) are facilitated by the medial pons. However, this area also may contain cells from which shivering could originate (Amini-Sereshki, 1977). The reticular formation of the medulla oblongata (MO) also may contain a controller capable of driving autonomic thermoregulatory responses independently of the PO/AH. Thus, thermal stimulation of the MO (Chai and Lin, 1972) produces appropriate autonomic responses, albeit the relation between these and medullary temperature (TMO) is not as precise as that between such responses and TPO/AH. Moreover, the effects of MO thermal stimulation persist and even are enhanced after PO/AH destruction (Lipton, 1973). Medullary lesions cause deficits in temperature regulation against both heat and cold (Lipton et al., 1974). It has been suggested that the MO may provide local temperature information to the PO/AH (Cabanac, 1970); or, it may be a separate, secondary thermoregulatory control with direct, extrahypothalamic links to thermoeffectors, but important only during extreme body temperature changes (Chai and Lin, 1973; Lipton, 1973). It normally may be tonically inhibited by the PO/AH directly via lateral pathways (Lipton et al., 1974); or it may be inhibited by the MRF alone (Chambers et al., 1974), the inhibitory influence of which in turn may be inhibited by the PO/AH (Satinoff, 1974).

Spinal cord.

The existence of thermosensitive structures in the spinal cord has been amply verified (reviewed by Simon, 1974). Both warm-and cool-responsive neurons have been identified. They are distributed over the length of the spinal cord (e.g., dogs [Simon et al., 1964]), or concentrated in its lower cervical and upper thoracic segments (e.g., guinea pigs [Wünnenberg and Brück, 1968a]). Their activation by changes in local temperature stimulates appropriate thermoeffector responses. Spinal heating of animals with transections of the anterolateral tracts anterior to the area of thermal stimulation does not suppress ambient cold-induced shivering (Wünnenberg and Brück, 1968b) or heat-induced panting (Kosaka et al., 1969), indicating that spinal temperature signals are conducted to the brainstem and integrated there to evoke thermoregulatory responses. Wünnenberg and Brück (1970) have traced these ascending channels to the AH. On the other hand, coordinated thermoeffector reactions also can be induced in spinalized and midbrain-transected preparations by thermal stimulation of the spinal cord (Thauer, 1935; Simon et al., 1966) or the skin (Kosaka and Simon, 1968), indicating the existence of independent thermoregulatory control functions at the spinal level as well.

Summarizing, autonomic thermoregulatory functions may be attributed to brain areas outside of the PO/AH. These mechanisms appear to be subsidiary controls, may have their own (direct?) links to thermoeffectors, and are capable of operating independently of the PO/AH, although they normally may be influenced by it through ascending and/or descending connections. Thus, the role of the PO/AH in temperature regulation may be seen as not essential, but nevertheless pre-eminent in the control of appropriate, coordinated, and low-threshold thermoregulatory responses. In this role, it receives afferent information from thermosensitive regions throughout the body, and is connected with all the thermoeffectors.

Possible independent receptor-effector loops.

However, other evidence suggests that the PO/AH may not be the dominant area of integrative control. Following earlier observations by Lipton et al. (1974), Gilbert and Blatteis (1977) found that the neural connections subserving heat and cold thermoeffectors, although closely arranged, nevertheless could be separated by precise microknife cuts. Thus, they localized different sites in the hypothalamus of rats which separately control different autonomic thermoregulatory functions, viz., cold-induced skin vasoconstriction in the PO, shivering activity in the PH, and heat-induced skin vasodilation in the AH or the MO. They, moreover, showed that the integrity of the PO is indispensable in rats for the control of cold-induced cutaneous vasoconstriction, but not for that of cold thermogenesis and heat-induced cutaneous vasodilation. They concluded that autonomic thermoregulatory mechanisms may be organized in separate receptor-effector pathways. Satinoff et al. (1976b) have reported that PO/AH lesions in rats produce deficits in autonomic cold defense mechanisms, the components of which recover in patterns that are independent of each other, but depend on the locus of the initial damage. A gradual recovery of cold tolerance after extensive hypothalamic lesions also has been noted by others (Hamilton and Brobeck, 1964; Chowers et al., 1972). Hence, these results suggest that individual components of the total pattern of thermoregulatory responses may be controlled separately at different sites in the brainstem. The disparate thermoregulatory effects of seemingly similar lesions observed by different workers may have been due to variations in the specific populations of temperature receptors and/or of pathways from these to thermoeffectors affected by the experimental procedures, variously affecting heat production or heat loss capacity in each case. (It should be noted in this context that the ventromedial region of the hypothalamus [just posterior to the AH] may modulate efferent peripheral sympathetic activity [Ban, 1975]) Each response in a pattern may have its own operating characteristics. The fact that thermoregulatory responses often occur together may be related to the intensity and locus of the activating signals; if adequate, they may stimulate them all (simultaneously?). Under conditions of moderate thermal stress, all thermoeffector responses do not, in fact, begin together, but rather appear in sequence (Blatteis, 1960). Thus, the recruitment of the various thermoeffector mechanisms into appropriate and coordinated autonomic thermoregulatory responses may involve the integration of afferent and efferent signals through functionally independent neural networks distributed from the PO/AH to the MO (and’ spinal cord?).

Behavioral Temperature Regulation

PO/AH control mechanisms.

The hypothalamus also is involved in the nervous control of behavioral thermoregulatory mechanisms. Postural adaptive reactions have been observed on warming (Hellström and Hammel, 1967) or cooling (Freeman and Davis, 1959) the hypothalamus. Again, the primary temperature controller may lie in the PO/AH region. To wit, warming or cooling the PO/AH elicits appropriate behavioral responses (reviewed by Cabanac, 1974; Satinoff and Hendersen, 1977). The magnitude of these changes is, in general, proportional to the displacement of TPOAH above or below specific thresholds (Laudenslager, 1976). Thus, behavioral thermoregulatory responses have operating characteristics similar to those that influence autonomic responses, and may be activated by the same elements, i.e., the two systems may be regulated by the same primary controller.

Extra-PO/AH control mechanisms.

However, like the autonomic, behavioral thermoregulatory responses also may not be integrated solely in the PO/AH. Thus, thermal stimulation of the PH elicits corrective behavioral thermoregulatory responses in monkeys (Adair, 1974), albeit not in rats (Lipton, 1971). On the other hand, thermal stimulation or local anesthesia of the MRF does not influence behavioral thermoregulation (Adair and Stitt, 1971; Lipton, 1971; Humphreys et al., 1976). However, heating or cooling the MO causes appropriate adaptive behaviors which parallel those induced by thermal stimulation of the PO/AH, but are independent of it because they still occur and even are enhanced after its destruction (Lipton, 1973). Similarly, thermal stimulation of the spinal cord evokes appropriate behavioral responses, generally identical with those induced by external or hypothalamic heating or cooling (Carlisle and Ingram, 1963).

In sum, as in the case of autonomic thermoregulation, there also exist multiple loci, from the PO/AH to the spinal cord, from which behavioral thermoregulatory responses can be elicited. While the neuronal elements regulating these two systems overlap at some sites, they appear to be completely separate at others. This would imply that the neural networks for each may be distinct.

Independence of autonomic and behavioral networks.

That this may be the case is supported by evidence that the two functions can be further dissociated. Thus, in rats, PO/AH lesions disrupt the autonomic, but not the behavioral, responses to exposure to cold (Rudiger and Seyer, 1965; Carlisle, 1969; Satinoff and Rutstein, 1970; Van Zoeren and Stricker, 1977) and to warm (Lipton, 1968; Stricker and Hainsworth, 1970; Toth, 1973) environments; the rats do not maintain their body temperatures. By contrast, lateral hypothalamic (LH) lesions impair behavioral thermoregulation in the cold (Rudiger and Seyer, 1965; Satinoff and Shan, 1971; Van Zoeren and Stricker, 1977) and in the heat (Hainsworth and Epstein, 1966), but do not affect autonomic regulation except transiently; these animals’ body temperatures are well maintained.

The findings that PO/AH lesions impair autonomic thermoregulatory responses are consistent with expectations (see above). The fact that this function survives after LH lesions, however, is unexpected, since the pathways for autonomic regulation against cold pass laterally from the PO/AH into the median forebrain bundle (MFB) and then to the LH (Sherwood et al., 1954; McCrum, 1953; Lipton et al., 1974; Gilbert and Blatteis, 1977), while those against heat occupy a more diffuse, dorso-lateral position (Gilbert and Blatteis, 1977; Lipton et al., 1974). In view of the apparent, relative discreteness of individual thermoreceptor-autonomic thermoeffector pathways (Gilbert and Blatteis, 1977), the discrepancy might be ascribed to the possibility that these gross lesions spared the relevant pathways in the LH. Indeed, conflicting results have been reported. Stricker and Hainsworth (1970) found that LH lesions of rats suppressed (autonomic) saliva secretion, but not (behavioral) saliva spreading (grooming) in a warm environment, while Laudenslager (1976) saw neither autonomic nor behavioral effects in squirrel monkeys after thermal stimulation of the LH. Humphreys et al. (1976) found that local LH anesthetization did not significantly affect behavioral thermoregulation, although the animals became hypothermic in a thermoneutral and hyperthermic in a warm environment.

Since the PO/AH-lesioned animals continue to perform their operant tasks, these behaviors could be initiated by structures outside of the PO/AH. It cannot be ascertained at present which of the potential loci, i.e., LH, PH, or MO, is responsible for the effects observed. Satinoff (1974) has suggested that the controllers of such behaviors may be located in the LH. However, other evidence has indicated that LH lesions may disrupt a common activational component of motivation. (It should be noted that all the above results are based on thermally motivated instrumental responding, i.e., operant behavior.) Thus, Stein (1964) has proposed that the MFB, which courses through both the LH and PH, may be part of a. motivational system which facilitates several operant behaviors. Indeed, besides motivated thermoregulatory behaviors, other non-thermoregulatory operant behaviors also can be disrupted by LH lesions (Teitelbaum and Epstein, 1962). Moreover, since not all these behaviors are affected equally by LH lesions, i.e., all possible combinations of losses can occur (Satinoff and Shan, 1971; Van Zoeren and Stricker, 1977), each component of these motivated behaviors may be independent of the others. This implies that each may pass through the LH by separate pathways, with thermoregulatory behavior being just one of these. Hence, if the effective part of the conscious perception of thermal states were the motivation for thermoregulatory behavior, then damage to the central controls of motivational activities could account for the decreased responding exhibited by LH-lesioned rats. Alternatively, this reduced behavior may reflect the wider sensorimotor dysfunctions characteristically produced by LH lesions (Stricker and Zigmond, 1976; Marshall and Teitelbaum, 1977); or it may reflect sensory deficits alone. Thus, the MFB may be part of a pathway relaying cutaneous thermal afferents to various parts of the hypothalamus (Gilbert and Blatteis, 1977). Therefore, animals with LH lesions may not be sensitive to peripheral cold stimuli and for that reason not press for heat in the cold until their internal temperature has fallen appreciably.

In summary, hypothalamic as well as extrahypothalamic areas may influence thermoregulatory behaviors, and not all the integration of this response mode may occur in the PO/AH. Moreover, although autonomic and behavioral thermoregulations probably possess common sources of information, they may not be integrated by a single controller. Indeed, observations in pigeons have revealed an antagonistic activation of autonomic and behavioral thermoregulatory defense responses during hypothalamic thermal stimulation (Schmidt, 1978). Hence, these two classes of regulation may be functionally and anatomically separate.

Independent neural loops.

The control system for behavioral thermoregulation, like that for autonomic thermoregulation, also may be organized into networks independent of each other. Thus, localized diathermic warming of various areas of the brainstem of rats has revealed that individual components of their behavioral response to heat are located in different, but partially overlapping, areas, viz., prone extension in the PO/AH region, grooming in the PH and the anterior ventral midbrain, and locomotion in the septal area, the ventromedial midbrain, and the dorsal medial MO (Roberts and Mooney, 1974). Lesioning of these areas affects only the specific responses localized therein (Roberts and Martin, 1977). A similar functional and anatomical separation between grooming and postural relaxation exists in the opossum (Roberts et al., 1969).

Fever: Localization of EP Action

It is generally agreed that fever is produced by the action of an endogenous pyrogen (EP) carried in the blood to the PO/AH region. Thus, EP elicits the most rapidly-developing and most intense febrile response when injected into the PO/AH (Cooper et al., 1967; Rosendorff and Mooney, 1971; Pittman et al., 1975; Jackson, 1967; Blatteis and Smith, 1979). However, EP also may act at extra-POAH sites to drive the fever-producing mechanisms. Ranson et al. (1939) reported that cats with hypothalamic lesions which impaired autonomic thermoregulation could still develop normal febrile reactions to systemic pyrogens. Similarly, AH and LH lesions do not alter the febrile response (Guerra and Barbour, 1943; Bard et al., 1970; Chambers et al., 1949; Haerting and Masserman, 1942). Relatively normal fevers also are produced following intravenous or intracerebroventricular endotoxin or EP after electrolytic destruction of the PO/AH (Andersson et al., 1965; Lipton and Trzcinka, 1976; Cooper et al., 1976). Moreover, a virtually normal febrile response can be obtained in low-decerebrate monkeys after severance of all hypothalamic connections to and from the lower brainstem (Liu and Shyy, 1980); but high-decerebrate cats, with the brainstem truncated just behind the hypothalamus, fail to develop fever (Chambers et al., 1949). Lipton et al. (1977) have reported a case of a patient with sarcoidosis involving marked symptoms of hypothalamic disorder, including profound dysthermia, who nevertheless was capable of developing infectious fevers. Other clinical cases of fever production despite extensive hypothalamic damage also have been described (Strauss and Globus, 1931; Gjersoe et al., 1950; Hockaday et al., 1962). The PH seems to be necessary for fever production since its destruction abolishes the febrile response (Cooper et al., 1976). However, direct microinjection of EP into the PH does not elicit a febrile response (Cooper et al., 1967; Rosendorff and Mooney, 1971; Blatteis and Smith, 1979). On the other hand, it has been reported (Allen, 1965) that an intravenous injection of ¹³¹I-labelled serum containing crude EP produced an intense localization of radioactivity in the PH of cats. The pons and medulla of rats and monkeys are insensitive to locally injected pyrogens (Lipton et al., 1973; Lipton and Trzcinka, 1976). Some febrile responsiveness to locally injected EP, albeit weaker and with a longer latency than that from the PO/AH, has been elicited from the MRF of rabbits (Rosendorff and Mooney, 1971), and also from the LH and MO of guinea pigs (Blatteis, 1980). The systemic injection of pyrogen depresses the firing rate of the warm-sensitive, and augments that of the cool-sensitive neurons of the PO/AH (Eisenman, 1969), the midbrain (Nakayama and Hori, 1973), and the MO (Sakata, 1979). Thus, in addition to an intra-PO/AH site, other sites may exist outside of the PO/AH and, indeed, outside of the hypothalamus, which are capable of mediating autonomic febrile responses.

Behavioral fever occurs in ectotherms, which lack autonomic thermoregulation (Kluger, 1979); it also occurs in neonatal endotherms before the capability for autonomic fever is developed (Satinoff et al., 1976a). Since the neuronal networks for behavioral and autonomic thermoregulation may be separate and independent, the EP receptor cells and/or the pathways to effectors mediating these two response modes also may be distinct. Indeed, in recent studies (Blatteis and Smith, 1980; Blatteis, 1980), EP injected into the PO and the LH elicited both autonomic and behavioral fevers, whereas only low-grade autonomic fevers were produced by intra-MO EP injections, suggesting that separate controllers for autonomic and behavioral fevers may exist. Finally, since both autonomic and behavioral thermoregulatory capabilities are present from birth, whereas autonomic fevers are not elicitable until later (Blatteis, 1975), it may be conjectured that the cells on which EP acts may be functionally and anatomically distinct from both the specific thermosensitive and the nonspecific thermosensitive (integrative?) neurons in the brainstem.

Conclusions

It is apparent that a coherent description of the central organization for thermal homeostasis is not yet possible. Although the notion that discrete central structures may have different thermoregulatory functions has been supported experimentally, studies to date have provided only clues to the major nuclear groups and afferent and efferent pathways involved. Thus, the location and boundaries of specific neural controllers and the organization of their interconnections in integrating the individual components of complex thermoregulatory responses as yet can be only tentatively described. The important characteristic that emerges is that, just as there are multiple temperature sensors and effectors, there are also multiple controllers, from the PO/AH to the spinal cord. Whether these function independently of each other or as subsidiary thermoregulatory mechanisms which become active when deprived from higher influences in the brainstem remains conjectural. In the latter case, a system governed by the PO/AH may be visualized, as was originally proposed by Thauer (1939). Under these conditions, the Jacksonian theory of hierarchical systems, i.e., alternating levels of inhibitory and facilitatory control of thermoregulatory responses, may operate, with higher-level controllers superimposed on lower ones to smooth and control them. In the former case, the neural structures controlling the various thermoregulatory responses may be anatomically and functionally separate, and organized in discrete afferent-efferent loops. Partial separation of autonomic and behavioral thermoregulatory controllers appears well established. Some evidence for the separation of individual components of autonomic and behavioral responses also exists. However, the degree to which they contribute to and the manner in which they are integrated in normal temperature regulation are unknown.

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CNS CONTROL OF BODY TEMPERATURE

JOHN T. STITT,     John B. Pierce Foundation Laboratory, Yale University School of Medicine, New Haven, Connecticut 06519, USA

Publisher Summary

This chapter discusses the central nervous system (CNS) control of body temperature. There is a multiplicative interaction between peripheral and central thermoreceptor inputs in the control of thermogenesis and perhaps other thermoregulatory effector outputs in mammals. Jacobson and Squires proposed a multiplicative relationship between ambient temperature and preoptic temperature in the regulation of oxygen consumption in cats. Bruck and Schwennicke demonstrated with the hyperbolic function that such a relationship existed between skin temperature, measured subcutaneously, and hypothalamic temperature in the control of nonshivering thermogenesis in the guinea pig. A similar type of control over heat production in the harbor seal has also been shown by Hammel et al. The chapter discusses a model that was proposed for the control of cold-induced thermogenesis in a rabbit. This model was predicated on a multiplicative interaction between mean skin temperature (Tsk) and preoptic anterior hypothalamic temperature (Thy). A distinctive feature of this model is that not only does it predict a decreasing hypothalamic thermosensitivity as the level of Tsk is increased but it also predicts that the Thy threshold for the onset of thermogenesis will decrease proportionately.

It has frequently been reported that there is a multiplicative interaction between peripheral and central thermoreceptor inputs in the control of thermogenesis and perhaps other thermoregulatory effector outputs in mammals. For example, Jacobson & Squires (1970) proposed a multiplicative relationship between ambient temperature and preoptic temperature in the regulation of oxygen consumption in cats. Brück & Schwennicke (1971), demonstrated with their now familiar hyperbolic function, that such a relationship existed between skin temperature, measured subcutaneously, and hypothalamic temperature in the control of non-shivering thermogenesis in the guinea pig. More recently, Hammel et al., (1977) have shown a similar type of control over heat production in the harbor seal, while Jessen (1977) has observed a multiplicative interaction between air temperature and hypothalamic temperature in the control of thermogenesis in the domestic goat.

In 1974 we proposed a model for the control of cold induced thermogenesis in the rabbit () and preoptic anterior hypothalamic temperature (Thy). The data from which this model was derived are shown in figure 1A, and the model can be approximated by the equation

Figure 1 sko and α in sk.

(1)

and Thyo = 45°C are shown in figures 1A and 1B.

is increased, but it also predicts that the Thy threshold for the onset of thermogenesis will decrease proportionately. We have attempted to use this model to understand how thermoreceptor inputs from the periphery and the hypothalamus might be organized in the regulation of body temperature.

More specifically, we have tested predictions which this model makes in order to ascertain the extent to which it might apply in the overall control of thermoregulation in the rabbit. sk. from 30.6°C to 39.5°C, there is a linear decrease in hypothalamic thermosensitivity; a result which is in accord with the prediction of the multiplicative model described by Eq.