Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts

Abstract

The regulation of food intake and energy balance relies on the dynamic integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic, cognitive, and emotional states. The paraventricular thalamus (PVT) is a central hub that, by integrating sensory, metabolic, and emotional states, may contribute to the regulation of feeding and homeostatic/allostatic processes. However, the underlying PVT circuits still remain elusive. Here, we aimed at unravelling the role of catecholaminergic (CA) inputs to the PVT in scaling feeding and metabolic efficiency. First, using region-specific retrograde disruption of CA projections, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius. Second, taking advantage of integrative calorimetric measurements of metabolic efficiency, we reveal that CA inputs to the PVT scale adaptive feeding and metabolic responses in environmental, behavioural, physiological, and metabolic stress-like contexts. Third, we show that hindbrain^TH →PVT inputs contribute to modulating the activity of PVT as well as lateral and dorsomedial hypothalamic neurons. In conclusion, the present study, by assessing the key role of CA inputs to the PVT in scaling homeostatic/allostatic regulations of feeding patterns, reveals the integrative and converging hindbrain^TH →PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts. KEY POINTS: The paraventricular thalamus (PVT) is known to receive projections from the hindbrain. Here, we confirm and further extend current knowledge on the existence of hindbrain^TH →PVT catecholaminergic inputs, notably from the locus coeruleus and the nucleus tractus solitarius, with the nucleus tractus solitarius representing the main source. Disruption of hindbrain^TH →PVT inputs contributes to the modulation of PVT neuron activity. Hindbrain^TH →PVT inputs scale feeding strategies in environmental, behavioural, physiological, and metabolic stress-like contexts. Hindbrain^TH →PVT inputs participate in regulating metabolic efficiency and nutrient partitioning in stress-like contexts. Hindbrain^TH →PVT inputs, directly and/or indirectly, contribute to modulating the downstream activity of lateral and dorsomedial hypothalamic neurons.

Keywords: food intake; hindbrain; homeostasis; indirect calorimetry; metabolism; paraventricular thalamus.