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

Abstract

AbstractThe 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 remain still elusive. Here, we aimed at unraveling 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 (NTS). 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, behavioral, physiological and metabolic stress-like contexts. Third, we show that hindbrainTH→PVT inputs contribute in modulating the activity of PVT as well as lateral (LH) and dorsomedial (DMH) hypothalamic neurons.In conclusion, this 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 hindbrainTH→PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts.Key pointsThe paraventricular thalamus (PVT) is known to receive projections from the hindbrain. Here, we confirm and further extend current knowledge on the existence of hindbrainTH→PVT catecholaminergic (CA) inputs, notably from the locus coeruleus (LC) and the nucleus tractus solitarius (NTS), with the NTS representing the main source.Disruption of hindbrainTH→PVT inputs contribute to the modulation of PVT-neurons activity.HindbrainTH→PVT inputs scale feeding strategies in environmental, behavioral, physiological and metabolic stress-like contexts.HindbrainTH→PVT inputs participate in regulating metabolic efficiency and nutrient partitioning in stress-like contexts.HindbrainTH→PVT, directly and/or indirectly, contribute in modulating the downstream activity of lateral (LH) and dorsomedial (DMH) hypothalamic neurons.