Baylor College of Medicine
Summary The neural circuitry mechanism underlying dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons located in the caudal ventral tegmental area (cVTA) that directly innervate DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake through an enhanced satiety response. Notably, this cohort of DAcVTA neurons activates immediately before the cessation of each feeding session. Acute inhibition of these DA neurons before the termination of combat substantially suppresses satiety and prolongs consummatory feeding. Activation of DRD1LPBN postsynaptic neurons inhibits feeding, while genetic deletion of Drd1 within the LPBN causes a strong increase in food intake and subsequent weight gain. Furthermore, DRD1LPBN signaling manifests the central mechanism in methylphenidate-induced hypophagia . In conclusion , our study illuminates a hindbrain DAergic circuit that controls feeding through dynamic regulation in the satiety response and food structure. |
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Like a good story, food has a beginning, a middle and an end. It begins with appetite that drives the search for food, continues with food intake, and ends when satiety sets in and food consumption stops.
At Baylor College of Medicine, Dr. Qi Wu, Dr. Yong Han and their colleagues have uncovered new aspects of the latter part of this story that relate to the little-known neural circuits and neurotransmitters involved in ending drug use. food.
The team discovered a novel circuit that connects a unique subset of dopamine -producing neurons to downstream neurons in the hindbrain (lower brainstem) and potently suppresses food intake by triggering satiety in mice .
They also found that the FDA-approved drug methylphenidate (MPH) mediates its notable weight-loss effect by activating this particular circuit, opening up the possibility that regulating this circuit may help people manage weight. The study appears in the journal Sciences Advances .
"Many people struggle with weight control, eating more than the body needs, adding extra pounds that can lead to obesity and a higher risk of serious diseases such as heart disease, stroke and type 2 diabetes," said Han, a postdoctoral associate in pediatrics-nutrition in Wu’s lab and the first author of this study. "Our lab is interested in improving our understanding of what happens in the brain during eating in the hope that our findings will one day help people better control their weight."
New insights into brain regulation of the satiety response:
"The current study deals with a circuit in the brain that helps precisely regulate the size of the portion of food consumed," said Wu, assistant professor of pediatrics-nutrition and corresponding author of the study. "It’s not about how the meal begins, but how it ends. It’s about the satiety response, which is as important as appetite."
Using several advanced techniques to study neuronal function, including cell-specific circuit mapping, optogenetics, and real-time recordings of brain activity, researchers discovered a novel neuronal circuit that connects a unique group of dopamine-producing neurons. called DA-VTA with a top-down objective. neurons known as DRD1-LPBN and regulate food consumption in mice.
The team examined the activities of the two sets of neurons while the mice ate. They observed that the activity of these DA-VTA neurons increased immediately before the animals stopped eating. When the researchers genetically inhibited these neurons, the animals prolonged their feeding, dramatically increasing portion size. This suggests that inhibition of the circuit prevented the satiety response. They also found that enhancing the activity of DRD1-LPBN neurons, which receive signals from DA-VTA neurons, robustly generated the meal termination response.
The researchers also found that the novel circuit mediated the weight loss effect associated with taking the drug MPH, which is approved to mitigate attention deficit hyperactivity disorder.
"Other brain circuits have been proposed to regulate eating, but the one we discovered is the first to be fully described to regulate portion size through dopamine signaling," Han said. "Our new study shows that a circuit "which connects neurons that produce dopamine, a chemical messenger previously known to regulate motivation and pleasure, has a new role in the control of eating by dynamically regulating the satiety response."
"Our finding that MPH suppresses feeding and reduces body weight in laboratory mice by strengthening the novel dopamine-supported circuit we discovered suggests a possible off-label application of a class of MPH and derivatives to combat obesity," he said. Wu. "This also has implications for the future development of circuit-based precision medicine that can deliver weight loss results more safely and effectively."
