Vertebrate behavioral thermoregulation: knowledge and future directions

Abstract

Thermoregulation is critical for survival across species. In animals, the nervous system detects external and internal temperatures, integrates this information with internal states, and ultimately forms a decision on appropriate thermoregulatory actions. Recent work has identified critical molecules and sensory and motor pathways controlling thermoregulation. However, especially with regard to behavioral thermoregulation, many open questions remain. Here, we aim to both summarize the current state of research, the "knowledge," as well as what in our mind is still largely missing, the "future directions." Given the host of circuit entry points that have been discovered, we specifically see that the time is ripe for a neuro-computational perspective on thermoregulation. Such a perspective is largely lacking but is increasingly fueled and made possible by the development of advanced tools and modeling strategies.

Keywords: behavior; circuits; computation; homeostasis; imaging; thermoregulation.

Fig. 1

Major thermoregulatory circuits in vertebrates. This figure illustrates major pathways and “relay stations” that have been identified to carry temperature information from the skin (detected by neurons from the trigeminal or DRG) to the preoptic area, which serves as a major hub for thermoregulation. Note that some details, such as the subdivision of the parabrachial nucleus as well as information on the output pathways, have been omitted for clarity. Red lines indicate a relay of “warmth,” and blue lines a relay of “cold.” Note that the central amygdaloid nucleus has only been shown to receive information about cold. Triangles indicate likely excitatory transmission and bars likely inhibitory transmission. The question marks are meant to illustrate integrative processes that are not fully understood.

Fig. 2

Interplay of thermal and inflammatory signals in the control of fever. (a) ${\mathrm{POA}}^{\mathrm{LPS}}$ neurons identified by Osterhout et al. increase their activity in response to prostaglandin E2 (PGE2) sensed via prostaglandin-EP2 receptors as well as in response to interleukin-$1\beta$ (not shown). These neurons are Galanin-ergic and send information to the hypothalamus and provide inhibition to warm-sensitive neurons marked by BDNF/PACAP, which can induce cold-seeking behavior. This provides a possible pathway to induce warm-seeking behaviors upon induction of inflammation. (b) PGE2 sensed by EP3 receptors directly inhibits GABAergic warm-sensitive neurons in the POA, which therefore has an effect similar to cooling and induces autonomous components of fever via known pathways as well as behavioral components via unknown pathways.^, How these two pathways both established through physiological and mutagenesis studies interact is currently unknown. PGE2, prostaglandin E2; EP2, PGE2-receptor 2; EP3, PGE2-receptor 3; POA, preoptic area; BDNF, brain-derived neurotrophic factor; PACAP, pituitary adenylate-cyclase activating polypeptide; WSN, warm sensitive neuron; Galn, galanin; LPS, lipopolysaccharides.

Fig. 3

Open questions in thermoregulation. (a): Thermosensory information passes through multiple multi-sensory relay stations (also see Fig. 1). If and how local processing shapes the signals within these structures is unclear, but it is conceivable that intermediate structures not only serve as passive relays of information. (b) While neurons have been found that can induce warm- and cold-seeking behaviors, how the animal actually accomplishes these tasks is unclear. This involves appropriate processing of sensory stimuli, adjusting behaviors based on external and internal thermosensory feedback, and importantly, limiting the cold- and warm-seeking behaviors themselves to avoid entering dangerous thermal regimes.