@article {69842, title = {Hedonic eating is controlled by dopamine neurons that oppose GLP-1R satiety.}, journal = {Science}, volume = {387}, year = {2025}, month = {2025 Mar 28}, pages = {eadt0773}, abstract = {

Hedonic eating is defined as food consumption driven by palatability without physiological need. However, neural control of palatable food intake is poorly understood. We discovered that hedonic eating is controlled by a neural pathway from the peri-locus ceruleus to the ventral tegmental area (VTA). Using photometry-calibrated optogenetics, we found that VTA dopamine (VTA) neurons encode palatability to bidirectionally regulate hedonic food consumption. VTA neuron responsiveness was suppressed during food consumption by semaglutide, a glucagon-like peptide receptor 1 (GLP-1R) agonist used as an antiobesity drug. Mice recovered palatable food appetite and VTA neuron activity during repeated semaglutide treatment, which was reversed by consumption-triggered VTA neuron inhibition. Thus, hedonic food intake activates VTA neurons, which sustain further consumption, a mechanism that opposes appetite reduction by semaglutide.

}, keywords = {Animals, Anti-Obesity Agents, Appetite, Dopaminergic Neurons, Eating, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptides, Male, Mice, Mice, Inbred C57BL, Neural Pathways, Optogenetics, Satiation, Satiety Response, Ventral Tegmental Area}, issn = {1095-9203}, doi = {10.1126/science.adt0773}, url = {https://doi.org/10.1126/science.adt0773}, author = {Zhu, Zhenggang and Gong, Rong and Rodriguez, Vicente and Quach, Kathleen T and Chen, Xinyu and Sternson, Scott M} } @article {65696, title = {Hindbrain double-negative feedback mediates palatability-guided food and water consumption.}, journal = {Cell}, volume = {182}, year = {2020}, month = {2020 Sep 17}, pages = {1589-1605}, abstract = {

Hunger and thirst have distinct goals but control similar ingestive behaviors, and little is known about neural processes that are shared between these behavioral states. We identify glutamatergic neurons in the peri-locus coeruleus (periLC neurons) as a polysynaptic convergence node from separate energy-sensitive and hydration-sensitive cell populations. We develop methods for stable hindbrain calcium imaging in free-moving mice, which show that periLC neurons are tuned to ingestive behaviors and respond similarly to food or water consumption. PeriLC neurons are scalably inhibited by palatability and homeostatic need during consumption. Inhibition of periLC neurons is rewarding and increases consumption by enhancing palatability and prolonging ingestion duration. These properties comprise a double-negative feedback relationship that sustains food or water consumption without affecting food- or water-seeking. PeriLC neurons are a hub between hunger and thirst that specifically controls motivation for food and water ingestion, which is a factor that contributes to hedonic overeating and obesity.

}, issn = {1097-4172}, doi = {10.1016/j.cell.2020.07.031}, author = {Gong, Rong and Xu, Shengjin and Hermundstad, Ann and Yu, Yang and Sternson, Scott M} } @article {46574, title = {Neurons for hunger and thirst transmit a negative-valence teaching signal.}, journal = {Nature}, volume = {521}, year = {2015}, month = {2015 Apr 27}, pages = {180-5}, abstract = {

Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational characteristics of two separate neuron populations that regulate energy and fluid homeostasis by using cell-type-specific activity manipulations in mice. We found that starvation-sensitive AGRP neurons exhibit properties consistent with a negative-valence teaching signal. Mice avoided activation of AGRP neurons, indicating that AGRP neuron activity has negative valence. AGRP neuron inhibition conditioned preference for flavours and places. Correspondingly, deep-brain calcium imaging revealed that AGRP neuron activity rapidly reduced in response to food-related cues. Complementary experiments activating thirst-promoting neurons also conditioned avoidance. Therefore, these need-sensing neurons condition preference for environmental cues associated with nutrient or water ingestion, which is learned through reduction of negative-valence signals during restoration of homeostasis.

}, doi = {10.1038/nature14416}, author = {Betley, J Nicholas and Xu, Shengjin and Cao, Zhen Fang Huang and Gong, Rong and Magnus, Christopher J and Yu, Yang and Sternson, Scott M} }