Shivering is an involuntary somatic motor response that occurs in skeletal muscles to produce heat during exposure to cold environments or during the development of fever. This study describes the brain circuitry mechanism that produces shivering. The reception of either cutaneous cool-sensory signals or pyrogenic signals by neurons in the preoptic area, a thermoregulatory and febrile centre, leads to activation of descending excitatory signalling through hypothalamic and medullary sites to drive shivering. Intriguingly, this central command pathway for shivering parallels that for sympathetically regulated non-shivering thermogenesis in brown adipose tissue. The present results promote our understanding of the brain mechanisms for thermal homeostasis that orchestrate the regulation of the somatic and autonomic motor systems to meet the critical demand for regulation of the body and brain temperatures. Abstract Shivering is a remarkable somatomotor thermogenic response that is controlled by brain mechanisms. We recorded EMGs in anaesthetized rats to elucidate the central neural circuitry for shivering and identified several brain regions whose thermoregulatory neurons comprise the efferent pathway driving shivering responses to skin cooling and pyrogenic stimulation. We simultaneously monitored parameters from sympathetic effectors: brown adipose tissue (BAT) temperature for non-shivering thermogenesis and arterial pressure and heart rate for cardiovascular responses. Acute skin cooling consistently increased EMG, BAT temperature and heart rate and these responses were eliminated by inhibition of neurons in the median preoptic nucleus (MnPO) with nanoinjection of muscimol. Stimulation of the MnPO evoked shivering, BAT thermogenesis and tachycardia, which were all reversed by antagonizing GABA A receptors in the medial preoptic area (MPO). Inhibition of neurons in the dorsomedial hypothalamus (DMH) or rostral raphe pallidus nucleus (rRPa) with muscimol or activation of 5-HT 1A receptors in the rRPa with 8-OH-DPAT eliminated the shivering, BAT thermogenic, tachycardic and pressor responses evoked by skin cooling or by nanoinjection of prostaglandin (PG) E 2, a pyrogenic mediator, into the MPO. These data are summarized with a schematic model in which the shivering as well as the sympathetic responses for cold defence and fever are driven by descending excitatory signalling through the DMH and the rRPa, which is under a tonic inhibitory control from a local circuit in the preoptic area. These results provide the interesting notion that, under the demand for increasing levels of heat production, parallel central efferent pathways control the somatic and sympathetic motor systems to drive thermogenesis.
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