Review articleCentral nervous system circuits that control body temperature
Introduction
Homeostatic control of body temperature is critical to the survival of mammals. Body temperature in mammals is generally maintained within a narrow range by the activation of multiple thermoeffector responses which are primarily under the control of central nervous system circuits. Important thermoeffector systems have evolved to maintain tissue temperatures at an appropriately elevated level to optimize enzymatic reactions and cellular function, while preventing dangerous elevations in body temperature that might compromise cellular function due to protein denaturation. Thermoregulatory behaviors, driven by cutaneous thermal receptors and motivated by thermal comfort, often comprise a first line of defense in maintaining body temperature in non-normothermic environments. The primary thermoeffector tissues include cutaneous blood vessels whose level of constriction determines whether the heat energy in warm blood will be radiated from the body to the environment or conserved in the body core. Salivary (in rodents) and sweat (in humans) glands provide fluid that dissipates body surface heat to the environment during evaporation. Thermogenesis due to skeletal muscle shivering and to the uncoupling of metabolic energy from ATP production in mitochondria, particularly prominent in brown adipose tissue, is the primary physiological heat source for cold defense. This review will provide an overview of the central neural circuits, from thermal afferents to thermoeffector tissues, that comprise the core neural pathways for the thermoregulatory responses.
Section snippets
Primary somatosensory neurons
Classic neurophysiological experiments have characterized two general classes of innocuous thermal afferent fibers, those activated by cooling and those activated by warming. The cold activated fibers are rapidly adapting A-delta fibers in humans and primates [19,43] and mostly c-fibers in other mammals such as, cats and rats [52]; these fibers respond with a dynamic activation during cooling and a sustained but diminished activation during stable cool thermal conditions. The warm activated
Preoptic area (POA) neurons integrate thermal sensory information to control thermoeffector output.
Since the discovery of the anterior hypothalamus/POA as a site at which thermoregulatory response could be elicited by local temperature changes [74] and the subsequent demonstration of directly thermosensitive neurons in this region [96], the POA has received significant attention as a major locus in thermoregulation. Changes in POA temperature can elicit a broad array of thermoregulatory responses including both heat defense responses such as sweating, saliva secretion, panting, and cutaneous
Efferent pathways controlling thermoeffectors
The efferent pathways controlling thermoeffectors can be defined into three general categories: thermogenic (BAT and shivering), vasomotor (cutaneous vasoconstrictor and cutaneous active vasodilator), and evaporative heat loss (sweating and saliva secretion) (Fig. 2). The thermogenic efferent pathways are largely overlapping and involve an inhibitory output from the POA that impinges on hypothalamic neurons in the dorsomedial hypothalamus. The thermogenesis-promoting neurons of the DMH activate
Febrile response
Prostaglandin E2 (PGE2) produced by endothelial cells in the POA in response to pyrogens (such as lipopolysaccharide, a component of the outer membrane of gram-negative bacteria) acts on EP3 receptors in the POA to elicit febrile responses [64,119]. Within the POA, EP3 receptors are located on neurons in the MPA and MnPO [89]. Some data have suggested that it is EP3 receptor activation in the MnPO that is necessary for febrile responses [64,136]. Alternatively, putative warm-sensitive neurons
Summary
The fundamental neural circuitry for body temperature homeostasis includes thermal afferent input impinging upon key neurons in the POA that integrate thermal input arriving via the spinal parabrachial-preoptic area afferent pathway (Fig. 1) with local POA temperature to elicit thermoeffector outputs. These thermoeffector outputs include unique neural pathways regulating BAT thermogenesis, shivering, CVC, evaporative heat loss via sweating (and saliva spreading in rodents), as well as
Acknowledgments
Support of the authors’ research that contributed to this review came from National Institutes of Health grants R01NS091066 (S.F.M.), R01NS40987 (S.F.M.), R01DK57838 (S.F.M.), R01DK065401 (C.J.M.) and R01DK112198 (C.J.M.).
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