September 5, 2024

A novel hypothalamic circuit and signaling mechanism for control of body temperature

How do warm-blooded organisms maintain core body temperature (CBT) within a narrow range, an essential requirement for survival? It has been established that the preoptic area of the hypothalamus plays an important role in CBT regulation by integrating peripheral thermal information and by sending efferent signals that control thermoregulatory mechanisms like thermogenesis, sweating, shivering etc. The decline in thermoregulation is closely associated with the age-related decline in human health.

A central question remains what are the cellular and molecular mechanisms that form the basis of the various thermoregulatory responses. Numerous neuromodulators and neurotransmitters have been identified as modulators of body temperature when administered exogenously, however, how they act when released endogenously is not known.

In his new paper published in eLife, Scintillon Institute scientist Iustin Tabarean describes a novel local circuit in the hypothalamus involved in the control of body temperature as well as a novel signaling mechanism consisting of the co-release of two neurotransmitters, GABA, an inhibitory neurotransmitter and neurotensin, an excitatory neuropeptide, by the same neurons.

The study also revealed that mice lacking the release of GABA from these neurons displayed drastically modified temperature responses to heat or cold stresses as well as to immune challenges.

Tabarean now plans to follow up directly on the multiple findings presented in this publication by exploring how other neuropeptides and neurotransmitters expressed in the preoptic area interact with the newly described circuit and their contributions to thermoregulation.

Opposing actions of co-released GABA and neurotensin on the activity of preoptic neurons and on body temperature by I.V. Tabarean, eLife https://elifesciences.org/articles/98677