Elsevier

Autonomic Neuroscience

Volume 85, Issues 1–3, 20 December 2000, Pages 18-25
Autonomic Neuroscience

Review
Neuronal circuitries involved in thermoregulation

https://doi.org/10.1016/S1566-0702(00)00216-2Get rights and content

Abstract

The body temperature of homeothermic animals is regulated by systems that utilize multiple behavioral and autonomic effector responses. In the last few years, new approaches have brought us new information and new ideas about neuronal interconnections in the thermoregulatory network. Studies utilizing chemical stimulation of the preoptic area revealed both heat loss and production responses are controlled by warm-sensitive neurons. These neurons send excitatory efferent signals for the heat loss and inhibitory efferent signals for the heat production. The warm-sensitive neurons are separated and work independently to control these two opposing responses. Recent electrophysiological analysis have identified some neurons sending axons directly to the spinal cord for thermoregulatory effector control. Included are midbrain reticulospinal neurons for shivering and premotor neurons in the medulla oblongata for skin vasomotor control. As for the afferent side of the thermoregulatory network, the vagus nerve is recently paid much attention, which would convey signals for peripheral infection to the brain and be responsible for the induction of fever. The vagus nerve may also participate in thermoregulation in afebrile conditions, because some substances such as cholecyctokinin and leptin activate the vagus nerve. Although the functional role for this response is still obscure, the vagus may transfer nutritional and/or metabolic signals to the brain, affecting metabolism and body temperature.

Introduction

The body temperature of homeothermic animals is regulated by behavioral and autonomic effector responses. The thermoreceptors for this regulation are distributed throughout the body: skin, the hypothalamus and other brain areas and the body core (Simon, 1974). Although this multiple input/output system is controlled primarily by the nervous system, the ‘neuronal circuit’ for thermoregulation remains poorly delineated. For example, while we know that the preoptic area (PO) definitely plays a central role in thermoregulation, we know little about what kinds of neurons in the PO are responsible for each effector response, and where these neurons project. The analysis of the neuronal circuit for thermoregulation had not made much progress during a couple of decades from the early 1960s. Kanosue et al. (1998) previously discussed the reasons. Briefly, neurophysiologists had concentrated on the analysis of membrane mechanisms of thermosensitivity and understanding the afferent system of thermal information from the skin. But in the last several years, new investigation approaches have helped breaking this stagnation, particularly for the efferent pathways from the PO.

Recent physiological studies have shown possible roles of the vagus nerve in thermoregulation. Especially, the subdiaphragmatic vagus nerves seems to work as important signal-transfer pathways from the periphery to the central nervous system (Székely and Romonovsky, 1998, Székely et al., 1997, Watkins et al., 1995), i.e. immunological reaction and/or metabolic information, which would be closely related to thermoregulation. However, we do not know well about how the vagus nerve participate in thermoregulation in contrast to enormous knowledge about its roles for digestive function. Studies a few decades ago showed the splanchnic nerves were the afferent pathway for the intra-abdominal thermoreceptors, but not the vagus nerve (Rawson and Quick, 1972, Riedel, 1976). These evidences might be a prime reason why the vagus nerve had long been neglected by most thermal physiologists. Studies to explore the vagal network for thermoregulation have just started.

In this review, we first discuss the neuronal circuit of thermoregulation, focusing new information relating to efferent pathways from the PO. Secondly, we refer to the roles of the vagus nerve as an afferent signal-pathway for thermoregulation. Because many reviewers in this volume write about the vagus nerve in relation to fever, we primarily discuss the role of the vagal afferent in themoregulation in afebrile condition.

Section snippets

Dominance of warm-sensitive neurons for detecting brain temperature

After discovery of thermosensitive neurons in the hypothalamus (Nakayama et al., 1961) neurophysiologists investigating thermoregulation directed their efforts to the analysis of these thermosensitive neurons. Their (implicit) assumption was that thermosensitivity is a distinctive characteristic of neurons playing a role in thermoregulation. Neurons displaying thermosensitivity, however, could be recorded anywhere in the brain, even in the cerebral cortex (Barker and Carpenter, 1970). Despite

Shivering

Shivering is involuntary tremor of skeletal muscles, which is caused not only by cold but also by other stimuli such as strong emotions. Cold-induced shivering can be inhibited by voluntary control to some extent. However, cold-induced shivering should be included in ‘autonomic’ thermoregulatory effector activities (IUPS Thermal Commission, 1987), since it is driven ‘involuntarily’ by cold signals from central and peripheral thermoreceptors. As noted above, the PO sends inhibitory efferent

Cutaneous blood flow

The PO is a strong thermosensitive site, eliciting skin vasodilation when it is heated (Ishikawa et al., 1984). As noted above, in rats this response is elicited mainly by the activation of warm-sensitive neurons (Zhang et al., 1995). Efferent pathways from the PO descend through the medial forebrain bundle (Kanosue et al., 1994b). Two different regions in the midbrain probably participate in vasomotor control neurons (Zhang et al., 1997). One extends from the caudal edge of the lateral

Anatomical aspect in the connection of the vagus nerve

Most of afferent axons in the vagi terminate in the nucleus of the solitary tract (NST), which is made up of small nerve cells, considerably smaller than those in the motor nucleus of the vagus (Norgren and Smith, 1988). The basic difference in the vagal afferents from other sensory nerves is that the peripheral distribution is quite large despite the central termination is small. From physiological view, there are many functional roles in the vagus nerve. Therefore, it is still difficult for

Vagal afferent signals relating afebrile thermoregulation

The vagal afferents play a crucial role for thermoregulation during fever (Watkins et al., 1995, Sehic and Blatteis, 1996, Romonovsky et al., 1997). We recently found that night-time body temperature in vagotomized rats was lower than that in control rats, while day time body temperature did not differ between the two groups (unpublished observation). In relation to these findings, antipyretic drugs have influences on normal body temperature, depending on the time of the day. That is, the

Metabolic information from the periphery to the brain

Some peripherally secreted substances, such as leptin and cholecystokinine (CCK) are closely related to metabolism and thermogenesis (Székely et al., 1994, Székely et al., 1997, Doring et al., 1998, Geiser et al., 1998) besides their food-satiety effects. Recent data show that the vagus nerve activity is altered by the presence of CCK and/or leptin (Grundy et al., 1995, Kurosawa et al., 1999, Shiraishi et al., 1999). These results may indicate that the vagus nerve is involved in transferring

Conclusions

Although some neurons of the efferent side in the thermoregulatory network have been identified, such as medullary premotor neurons for vasomotor control and reticulospinal neurons in the shivering pathway, our knowledge of thermoregulatory circuit is still fragmentary. But we are certainly at the door to the new era of research in thermoregulatory system.

As for the afferent side of the thermoregulation network, thermo-sensors are located all around in the body. Besides these neurons, the vagus

Acknowledgements

We thank Professor L.I. Crawshaw for his critical reading and comments on this manuscript. This study was supported in part by a Grant-in-Aids for Scientific Research from the Ministry of Education, Science and Culture of Japan (Grants No. 04454143, 12307001 and 09470016).

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