Descending raphe circuits for adaptive thermogenesis

• Applicants: Henning Fenselau, Ph.D.; Professor Dr. Peter Kloppenburg
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505389599

Adaptive thermogenesis is a vital homeostatic process for body temperature regulation. Because it increases systemic energy expenditure, adaptive thermogenesis represents a significant factor in energy balance. Descending sympathetic pathways, which consist of brain neurocircuits projecting to spinal sympathetic preganglionic neurons, connect the brain to peripheral thermogenic tissues, and thereby critically contribute to the central control of adaptive thermogenesis. Previous histological and pharmacological studies identified the raphe pallidus (rPa) of the brainstem as a key component of these thermogenic pathways. However, the specific rPa neuron population, which sends descending projections to the spinal cord, and their downstream sympathetic neurocircuits controlling adaptive thermogenesis remain to be elucidated. Further, the neuroactive chemicals (i.e., neurotransmitters and neuromodulators) conveying thermogenic signals across synapses between rPa neurons and postsynaptic spinal sympathetic preganglionic neurons remain unclear. The latter is of particular interest because rPa neurons express various potential neurotransmitters and neuromodulators that are known to have a role in regulating energy expenditure and body weight – such as thyrotropin-releasing hormone and serotonin. Therefore, the overarching aims of this comprehensive research proposal are to define the thermoregulatory function of molecularly defined rPa neurons, and to elucidate the physiological function of the neuroactive chemicals they release onto spinal sympathetic preganglionic neurons. These complementary aims will collectively gain greater insights into the integral components of sympathetic pathways in controlling adaptive thermogenesis, and brain control of energy balance and body weight homeostasis.

• DFG Programme: Research Grants