Paraventricular Thalamic Control of Food Intake and Reward: Role of Glucagon-Like Peptide-1 Receptor Signaling

Paraventricular thalamic nucleus (PVT) neurons receive hindbrain and hypothalamic inputs, and project to forebrain sites involved in reward and motivation function. The role of PVT in energy balance and reward control is however understudied. Given that PVT neurons express glucagon-like peptide-1 re...

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Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2017-11, Vol.42 (12), p.2387-2397
Main Authors: Ong, Zhi Yi, Liu, Jing-Jing, Pang, Zhiping P, Grill, Harvey J
Format: Article
Language:English
Subjects:
Activation
Animals
Body weight
Conditioning
Diet, High-Fat - psychology
Diet, High-Fat - trends
Eating - physiology
Energy balance
Excitability
Feeding behavior
Fibers
Food
Food intake
Food preferences
Forebrain
Glucagon
Glucagon-like peptide 1
Glucagon-Like Peptide-1 Receptor - physiology
High fat diet
Hindbrain
Hypothalamus
Innervation
Male
Mice
Mice, Inbred C57BL
Midline Thalamic Nuclei - physiology
Motivation
Neurons
Nuclei (cytology)
Nucleus accumbens
Organ Culture Techniques
Original
Place preference conditioning
Rats
Rats, Sprague-Dawley
Reinforcement
Reinstatement
Reward
Signal Transduction - physiology
Solitary tract nucleus
Sucrose
Sugar
Thalamus
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Summary:Paraventricular thalamic nucleus (PVT) neurons receive hindbrain and hypothalamic inputs, and project to forebrain sites involved in reward and motivation function. The role of PVT in energy balance and reward control is however understudied. Given that PVT neurons express glucagon-like peptide-1 receptors (GLP-1R), which are critical to feeding and body weight control, we tested the hypothesis that PVT GLP-1R signaling contributes to food intake and reward inhibition. To assess the hypothesis, behavioral tests including chow and high-fat diet intake, meal patterns, conditioned place preference for high-fat food, cue-induced reinstatement of sucrose-seeking, and motivation to work for sucrose were employed following intra-PVT delivery of either GLP-1R agonist, exendin-4 (Ex4), or GLP-1R antagonist, exendin-9-39 (Ex9). Anatomical and electrophysiological experiments were conducted to examine the neural connections and cellular mechanisms of GLP-1R signaling on PVT-to-nucleus accumbens (NAc) projecting neurons. PVT GLP-1R agonism reduced food intake, food-motivation, and food-seeking, while blocking endogenous PVT GLP-1R signaling increased meal size and food intake. PVT neurons receive GLP-1 innervation from nucleus tractus solitarius preproglucagon neurons that were activated by food intake; these GLP-1 fibers formed close appositions to putative GLP-1R-expressing PVT cells that project to the NAc. Electrophysiological recordings of PVT-to-NAc neurons revealed that GLP-1R activation reduced their excitability, mediated in part via suppression of excitatory synaptic drive. Collectively, these behavioral, electrophysiological and anatomical data illuminate a novel function for PVT GLP-1R signaling in food intake control and suggest a role for the PVT-to-NAc pathway in mediating the effects of PVT GLP-1R activation.
ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2017.150