Received March 10, 2008
Revised April 7, 2008
Accepted after revision May 8, 2008

¹ Oregon Hlth & Sci Univ

^* To whom correspondence should be addressed. E-mail: morrisos{at}ohsu.edu.

	Abstract

Thermogenesis, the production of heat energy, is an essential component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature and plays a key role in elevating body temperature during the febrile response to infection. The primary sources of neurally-regulated metabolic heat production are mitochondrial oxidation in brown adipose tissue, increases in heart rate and shivering in skeletal muscle. Thermogenesis is regulated in each of these tissues by parallel networks in the central nervous system which respond to feedforward afferent signals from cutaneous and core body thermoreceptors and to feedback signals from brain thermosensitive neurons to activate the appropriate sympathetic and somatic efferents. This review summarizes the research leading to a model of the feedforward reflex pathway through which environmental cold stimulates thermogenesis and includes the influence on this thermoregulatory network of the pyrogenic mediator, prostaglandin E2, to increase body temperature. The cold thermal afferent circuit from cutaneous thermal receptors, through second-order thermosensory neurons in the dorsal horn of the spinal cord ascends to activate neurons in the lateral parabrachial nucleus which drive GABAergic interneurons in the preoptic area to inhibit warm-sensitive, inhibitory output neurons of the preoptic area. The resulting disinhibition of thermogenesis-promoting neurons in the dorsomedial hypothalamus and possibly of sympathetic and somatic premotor neurons in the rostral ventromedial medulla, including the raphe pallidus, activates excitatory inputs to spinal sympathetic and somatic motor circuits to drive thermogenesis.

Key Words: Hypothalamus, Serotonin, Thermoregulation