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

Abstract

Aim: The regulation of food intake and energy balance relies on the integration of exteroceptive and interoceptive signals monitoring nutritional, metabolic and emotional states. This study aims at unraveling the role of catecholaminergic (CA) inputs to the paraventricular thalamus (PVT) in scaling feeding and metabolic efficiency. Methods: To tackle this question, a region-specific retrograde disruption of PVT CA inputs was performed. Behavioral tests and in vivo calorimetric technologies were mobilized to study the adaptive strategies underlying feeding, metabolic efficiency and nutrient partitioning. Moreover, immunofluorescence investigations were conducted to identify the sources of TH-neurons projecting to the PVT and to reveal the molecular pattern of neuronal activation (cFos) in the PVT as well as in homeostasis-related regions of the hypothalamus. Results: First, we show that PVT CA inputs mainly arise from the hindbrain, notably the locus coeruleus (LC) and the nucleus tractus solitarius (NTS). Second, we reveal that PVT CA inputs contribute to feeding strategies and metabolic efficiency in environmental, behavioral, physiological and metabolic stress-like contexts. Third, we show that PVT CA inputs contribute in modulating the activity of PVT as well as lateral (LH) and dorsomedial (DMH) hypothalamic neurons. Conclusion: This study, by assessing the key role of PVT CA inputs in scaling homeostatic and allostatic regulations of feeding patterns, reveals the integrative and converging hindbrain→PVT paths that contribute to whole-body metabolic adaptations in stress-like contexts.