Central Mechanisms for Thermoregulation

Abstract

Maintenance of a homeostatic body core temperature is a critical brain function accomplished by a central neural network. This orchestrates a complex behavioral and autonomic repertoire in response to environmental temperature challenges or declining energy homeostasis and in support of immune responses and many behavioral states. This review summarizes the anatomical, neurotransmitter, and functional relationships within the central neural network that controls the principal thermoeffectors: cutaneous vasoconstriction regulating heat loss and shivering and brown adipose tissue for heat production. The core thermoregulatory network regulating these thermoeffectors consists of parallel but distinct central efferent pathways that share a common peripheral thermal sensory input. Delineating the neural circuit mechanism underlying central thermoregulation provides a useful platform for exploring its functional organization, elucidating the molecular underpinnings of its neuronal interactions, and discovering novel therapeutic approaches to modulating body temperature and energy homeostasis.

Improved neural control of body temperature following heat acclimation in humans

“…Our current understanding of the neural circuitries involved in autonomic temperature regulation is largely based on rodent models (Madden & Morrison, 2019; Morrison & Nakamura, 2019). Although, unlike humans, rodents do not employ active cutaneous vasodilatation nor eccrine sweat production as heat loss thermoeffectors, insight can still be drawn from these models to advance potential mechanisms by which the neural control of body temperature is improved with heat acclimation.…”

Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus

“…py: pyramidal tract, 7: facial motor nucleus that iv 5-HT leads to a nearly complete inhibition of coldevoked BAT SNA by influencing the balance of excitatory and inhibitory inputs to thermogenesis-promoting neurones in the DMH, a key BAT excitatory site in the CNS circuit through which cold thermoreceptors in the skin drive BAT and shivering thermogenesis. 18,20,38 Specifically, our data indicate that the effect of iv 5-HT to reverse the cold-defensive activation of BAT thermogenesis is mediated by an augmented inhibitory input to the DMH neurones that provide an essential excitation to BAT sympathetic premotor neurones in the rRPa that mediate the increased BAT thermogenesis in response to a fall in skin/core temperatures. 7,20,26,43 The hypothermic effects of systemic administration of 5HT 1A R agonists in humans 44,45 is mimicked in rodents 31,32,46,47 and has been studied in part because of the hypothermic effects of some antidepressant and antianxiety drugs, 27,28 including 8-OH-DPAT.…”

“…18,20,38 Specifically, our data indicate that the effect of iv 5-HT to reverse the cold-defensive activation of BAT thermogenesis is mediated by an augmented inhibitory input to the DMH neurones that provide an essential excitation to BAT sympathetic premotor neurones in the rRPa that mediate the increased BAT thermogenesis in response to a fall in skin/core temperatures. 7,20,26,43 The hypothermic effects of systemic administration of 5HT 1A R agonists in humans 44,45 is mimicked in rodents 31,32,46,47 and has been studied in part because of the hypothermic effects of some antidepressant and antianxiety drugs, 27,28 including 8-OH-DPAT. [29][30][31][32] 8-OH-DPAT-induced antidepressant effects and hypothermia are prevented by systemic administration of centrally active 5HT 1A R antagonists.…”

“…These studies describe a novel role of systemic 5‐HT in inhibiting the sympathetic outflow to BAT and thereby reducing the BAT thermogenesis that contributes to the maintenance of body temperature during cold exposure. We established that iv 5‐HT leads to a nearly complete inhibition of cold‐evoked BAT SNA by influencing the balance of excitatory and inhibitory inputs to thermogenesis‐promoting neurones in the DMH, a key BAT excitatory site in the CNS circuit through which cold thermoreceptors in the skin drive BAT and shivering thermogenesis . Specifically, our data indicate that the effect of iv 5‐HT to reverse the cold‐defensive activation of BAT thermogenesis is mediated by an augmented inhibitory input to the DMH neurones that provide an essential excitation to BAT sympathetic premotor neurones in the rRPa that mediate the increased BAT thermogenesis in response to a fall in skin/core temperatures …”

“…Having established that iv 5‐HT does not inhibit BAT thermogenesis via 5‐HT 1A R in the rRPa, we sought to determine where within the core thermoregulatory pathway controlling BAT SNA, iv 5‐HT might be acting to inhibit BAT thermogenesis. As a first step, we determined if iv 5‐HT was acting at a site in the BAT sympathetic efferent pathway distal to the rRPa.…”