A thermosensory pathway mediating heat-defense responses

Abstract

Afferent neural transmission of temperature sensation from skin thermoreceptors to the central thermoregulatory system is important for the defense of body temperature against environmental thermal challenges. Here, we report a thermosensory pathway that triggers physiological heat-defense responses to elevated environmental temperature. Using in vivo electrophysiological and anatomical approaches in the rat, we found that neurons in the dorsal part of the lateral parabrachial nucleus (LPBd) glutamatergically transmit cutaneous warm signals from spinal somatosensory neurons directly to the thermoregulatory command center, the preoptic area (POA). Intriguingly, these LPBd neurons are located adjacent to another group of neurons that mediate cutaneous cool signaling to the POA. Functional experiments revealed that this LPBd–POA warm sensory pathway is required to elicit autonomic heat-defense responses, such as cutaneous vasodilation, to skin-warming challenges. These findings provide a fundamental framework for understanding the neural circuitry maintaining thermal homeostasis, which is critical to survive severe environmental temperatures.

Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature

“…Consistent with this hypothesis, tract-tracing studies in the rodent have shown that KNDy neurons project to structures critical for the regulation of body temperature (22,23) including the median preoptic nucleus (MnPO), an important component of a thermosensory heat-defense pathway (24). Moreover, pharmacological activation of NK 3 R-expressing neurons in the MnPO elicits a robust decrease in T CORE and alters tail skin vasomotion (25).…”

“…Therefore, in KNDy-ablated rats, removal of an excitatory input to NK 3 Rexpressing warm-sensitive medial preoptic neurons could explain the lower levels of tail skin vasodilatation. KNDy neurons could also influence tail vasomotion via projections to the MnPO, a major component of a thermosensory pathway regulating heatdefense effectors (24). MnPO Fos expression is modulated by changes in T AMBIENT or chronic E 2 treatment, implicating this nucleus as a site for integrating thermoregulatory and reproductive functions (37).…”

“…Moreover, focal microinfusion of an NK 3 R agonist activates MnPO neurons (as measured by Fos), elicits a robust drop in T CORE and inhibits sympathetic vasoconstriction (25). MnPO neurons project to other thermoregulatory regions of the hypothalamus (24,44,45) as well as neurons in the ventromedial medulla controlling tail vasomotion (42,(46)(47)(48). Thus, removal of excitatory KNDy neuron projections to the MnPO or medial preoptic area (or both) could provide a mechanism for the lower levels of tail skin vasodilatation in KNDy-ablated rats.…”

“…MnPO neurons express NK 3 R and pharmacological activation of these neurons reduces body temperature (25). The MnPO receives information from warm-sensitive, cutaneous thermoreceptors and projects to CNS centers to modulate heatdissipation effectors (24,42). (B) Effects of ovariectomy on serum LH and tail skin vasodilatation: Loss of E 2 after ovariectomy markedly increases NKB and kisspeptin gene expression in KNDy neurons (57,58), increases GnRH secretion into the portal capillaries (63) and LH secretion from the anterior pituitary gland.…”

Intrahypothalamic pituitary adenylate cyclase-activating polypeptide regulates energy balance via site-specific actions on feeding and metabolism

“…Given their effect on feeding, the PVN and VMN may be significant efferent targets of the LPB whereby LPB disinhibition could lead to increased excitation of these areas and anorexia. Furthermore, the LPB are critical structures in the thermoregulation pathway (41,42), thereby positioning the VMN as potential downstream targets of LPB signaling that, in turn, could modulate thermogenic responses.…”