Summary: A new study has revealed how brain circuits and neurotransmitters regulate meal initiation, offering insights into obesity management.
Researchers identified serotonin neurons in the midbrain’s dorsal Raphe nucleus (DRN) as key players, inhibited by GABA and dopamine when hunger strikes. This inhibition lowers serotonin levels, triggering feeding behavior, while satiety reverses the process. Notably, GABA and dopamine synergize for more profound effects on serotonin suppression.
These findings provide a deeper understanding of feeding regulation, informing potential therapies for obesity. Future research will explore how other feeding phases are governed by neural circuits.
Key Facts:
- Neurotransmitter Synergy: GABA and dopamine synergistically inhibit serotonin neurons during hunger, promoting meal initiation.
- Serotonin’s Role: Serotonin levels rise post-meal to curb further feeding, highlighting its dual role in hunger and satiety.
- Obesity Insight: Understanding these mechanisms could lead to improved obesity treatments targeting specific feeding phases.
Source: Baylor College of Medicine
When you are feeling hungry, the brain takes the necessary steps toward consuming a meal.
Many of these steps are not well known, but a new study published in the journal Metabolism by researchers at Baylor College of Medicine and the University of Texas Health Science Center at Houston reveals brain circuits and chemical messengers that contribute to the regulation of meal initiation and food intake.
The findings have implications for the development of improved therapies to manage obesity, a worldwide epidemic.
“It’s well known that serotonin, a neurotransmitter in the brain, can suppress food intake. This finding led to the development of drugs that interact with serotonin or its receptors to regulate food consumption and obesity,” said corresponding author Dr. Yong Xu, professor of pediatrics – nutrition and associate director of basic sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor.
“However, some of these drugs have unwanted side effects, and they are no longer offered to patients. There is a need to better understand how the brain regulates food intake to improve drug design.”
The Xu lab and colleagues have been studying the role of serotonin on feeding control for quite a long time. In this study, they focused on a little-known component of the serotonin regulation of food intake.
They looked for brain circuits and neurotransmitters that regulate the activity of serotonin-producing neurons, activating or inhibiting them at the appropriate periods to reach balanced food consumption.
“We asked, how can we leverage this system to regulate feeding?” Xu said.
Serotonin is primarily synthesized by neurons in the dorsal Raphe nucleus (DRN) in the midbrain. Serotonin neurons in the DRN project to numerous brain regions, including the arcuate of the hypothalamus (ARH).
The team showed that the ARH circuit and two neurotransmitters, GABA and dopamine, play a key role in meal initiation.
“Working with animal models, we found that when the animals are hungry, serotonin-producing neurons in the DRN are inhibited by GABA and dopamine. This reduces the levels of serotonin in the brain, which allows the initiation of a meal,” Xu explained.
“As the animals feed and reach satiety, the inhibitory signals on serotonin neurons are reduced and more serotonin is produced to inhibit feeding via projections to the ARH.”
“What’s unique about this is that GABA and dopamine act synergistically – when both are present, serotonin neurons appear to be more inhibited than when only one of the neurotransmitters is present,” Xu said.
This work is important because it improves our understanding of how the brain manages body weight and feeding, specifically the roles of neurotransmitters in a specific phase of feeding behavior, meal initiation. This knowledge can inform the development of improved obesity drugs.
“Looking forward, we are interested in identifying signals that regulate the other phases of feeding,” Xu said.
Other contributors to this work include Kristine M. Conde, Huey Zhong Wong, Shuzheng Fang, Yongxiang Li, Meng Yu, Yue Deng, Qingzhuo Liu, Xing Fang, Mengjie Wang, Yuhan Shi, Olivia Z. Ginnard, Yuxue Yang, Longlong Tu, Hesong Liu, Hailan Liu, Na Yin, Jonathan C. Bean, Junying Han, Megan E. Burt, Sanika V. Jossy, Yongjie Yang, Qingchun Tong, Benjamin R. Arenkiel, Chunmei Wang and Yang He. The authors are affiliated with Baylor College of Medicine or the University of Texas Health Science Center at Houston.
Funding: This work was supported by USDA/CRIS (grants 51000-064-01S, 3092-51000-062-04(B)S), National Institutes of Health (grants R01DK120858, F32DK134121, R01DK131446) and American Heart Association (grant 23POST1030352).
About this neuroscience and hunger research news
Author: Taylor Barnes
Source: Baylor College of Medicine
Contact: Taylor Barnes – Baylor College of Medicine
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Serotonin neurons integrate GABA and dopamine inputs to regulate meal initiation” by Yong Xu et al. Metabolism
Abstract
Serotonin neurons integrate GABA and dopamine inputs to regulate meal initiation
Obesity is a growing global health epidemic with limited orally administered therapeutics.
Serotonin (5-HT) is one neurotransmitter which remains an excellent target for new weight-loss therapies, but a gap remains in understanding the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation.
Using an optogenetic feeding paradigm, we showed that the 5-HTDRN➔arcuate nucleus (ARH) circuit plays a role in meal initiation.
Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response can be enhanced by hunger.
Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process.
Finally, we identified the role of dopaminergic inputs via dopamine receptor D2 in enhancing the response to GABA-induced feeding.
Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, for the initiation of a meal.
