A thermosensory pathway that controls body temperature

Abstract

Defending body temperature against environmental thermal challenges is one of the most fundamental homeostatic functions governed by the nervous system. Here we show a novel somatosensory pathway, which essentially constitutes the afferent arm of the thermoregulatory reflex triggered by cutaneous sensation of environmental temperature changes. Using rat in vivo electrophysiological and anatomical approaches, we revealed that lateral parabrachial neurons play a pivotal role in this pathway by glutamatergically transmitting cutaneous thermosensory signals received from spinal somatosensory neurons directly to the thermoregulatory command center, preoptic area. This feedforward pathway mediates not only sympathetic and shivering thermogenic responses but also metabolic and cardiac responses to skin cooling challenges. Notably, this 'thermoregulatory afferent' pathway exists in parallel with the spinothalamocortical somatosensory pathway mediating temperature perception. These findings make an important contribution to our understanding of both the somatosensory system and thermal homeostasis-two mechanisms fundamental to the nervous system and to our survival.Even during rapid changes in environmental temperature, the body temperature of homeothermic animals, including humans, is maintained within the narrow range necessary for optimal cellular and molecular functions. How the nervous system functions to defend body temperature against environmental thermal challenges remains a fundamental question in physiology 1,2 . The preoptic area (POA) is the thermoregulatory center providing command signals descending to peripheral effectors 1,3-6 . To evoke behavioral, autonomic, somatic and hormonal responses counteracting changes in environmental temperature before they impact body core temperature, thermoregulatory command neurons in the POA need to receive feedforward signaling of environmental temperature information from skin thermoreceptors through the spinal and trigeminal dorsal horns 3,5-8 . However, the neural substrate for the ascending thermoregulatory feedforward pathway, especially the essential central mechanism linking the second order somatosensory neurons in the dorsal horn to the POA has yet to be identified.The best-known central pathway for somatosensory signaling of cutaneous thermal sensation is the spinothalamocortical pathway, in which signals from skin thermoreceptors are transmitted through a direct projection from the dorsal horn to the thalamus and then relayed to the primary somatosensory cortex 9,10 . Although the spinothalamocortical pathway is responsible for perception and discrimination of cutaneous temperature 9,10 , it is unknown whether this pathway contributes to homeostatic responses against changes in environmental

A thermosensory pathway mediating heat-defense responses

“…S4C). The average antidromic latency and estimated conduction velocity of these warm-responsive neurons were 19.4 ± 1.7 ms and 0.54 ± 0.06 m/s, respectively, values that were not significantly different from those of cool-responsive, POA-projecting neurons recorded in the LPBel (20.9 ± 0.9 ms and 0.45 ± 0.02 m/s, n = 11, respectively; P > 0.05, two-tailed unpaired t test) (8). The remaining three antidromically activated LPB neurons were not exclusively localized within the LPBd (Fig.…”

“…In contrast, following cold exposure (4°C), Fos expression was detected in the CTb-positive cluster in the LPBel as well as in some spread neurons in the central part of the LPB (LPBc) but was limited to very few neurons in the LPBd (Figs. S1 D and G and S2 D and G) (8). Following exposure to the control temperature (24°C), only a few doublelabeled neurons were seen in either the LPBd or the LPBel (Fig.…”

“…The feedforward signaling of environmental temperature from the skin to the POA is important to evoke rapid physiological thermoregulatory responses that defend body temperature against changes in environmental temperature before they impact internal thermal homeostasis (3,(5)(6)(7). We recently identified a cool sensory pathway that mediates feedforward signaling for evoking thermoregulatory responses to environmental cooling challenges (8). The signals of cutaneous cool sensation that are transmitted from somatosensory neurons in the spinal dorsal horn activate neurons in the external lateral part of the parabrachial nucleus (LPBel), which then provide glutamatergic excitation to a midline portion of the POA that is centered within the median preoptic nucleus (MnPO) (8).…”

“…We recently identified a cool sensory pathway that mediates feedforward signaling for evoking thermoregulatory responses to environmental cooling challenges (8). The signals of cutaneous cool sensation that are transmitted from somatosensory neurons in the spinal dorsal horn activate neurons in the external lateral part of the parabrachial nucleus (LPBel), which then provide glutamatergic excitation to a midline portion of the POA that is centered within the median preoptic nucleus (MnPO) (8). Importantly, autonomous thermoregulation does not require thermosensory signaling in the spinothalamocortical pathway (8), which mediates the perception and discrimination of skin temperature changes (9).…”

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.…”