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Ghrelin and Brain Cells Control Meal Time

How feeding behavior is influenced by the hormone ghrelin in mice has been illuminated by a recent study.

The activation of specific neurons in the amygdala, a region primarily studied in the context of fear and reward, is prompted by ghrelin, resulting in food consumption and the experience of hunger and satisfaction.

Nine different cell clusters in the amygdala, which regulate appetite, were identified in the study, with the activation of those cells marked by the presence of protein Htr2a. By comprehending these mechanisms, insights into pathological eating behaviors and potential therapeutic solutions can be gained.

  • Specific neurons in the amygdala are activated by ghrelin, a hormone released during fasting or hunger, leading to food consumption and the generation of feelings associated with hunger and reward.
  • The amygdala consists of nine different cell clusters, each with varying roles in promoting or inhibiting appetite.
  • Brain circuits that confer rewards are enhanced by ghrelin, potentially motivating additional food consumption, especially in less severe hunger situations.

Knowing when it’s time for a meal – and when to stop eating again – is important for survival and maintaining health, both for humans and animals.

The regulation of feeding behavior in mice was investigated by researchers at the Max Planck Institute for Biological Intelligence. It was found that specialized nerve cells in a brain region known as the amygdala are activated by the hormone ghrelin.

In this case, the interaction between ghrelin and the specialized neurons leads to food consumption and the conveyance of hunger, as well as the pleasant and rewarding feelings associated with eating.

Hunger, a powerful sensation with significant biological foundations, serves as a signal for the body to search for food, which is crucial for preventing starvation and ensuring survival. When food cravings arise due to hunger, our body rewards us with pleasant feelings and a general state of happiness when we finally get to eat.

The eating behavior of humans and animals, along with the corresponding sensations, is orchestrated by a network of brain circuits and signaling pathways. A prominent participant in this network is the hormone ghrelin, which is released by stomach cells during hunger or fasting and promotes feeding behavior.


The brain networks underlying feeding behavior in mice are studied by the department of Rüdiger Klein at the Max Planck Institute for Biological Intelligence.

For this purpose, a comprehensive analysis of the various cell types in the central amygdala, a brain region, was conducted by the researchers.

“In the past, the amygdala was primarily examined in the context of emotions such as fear and reward, while the regulation of feeding was believed to occur in different brain areas, such as the hypothalamus,” explains Christian Peters, a postdoctoral researcher in the department.

Cell Clusters

Nine different cell clusters were analyzed by Peters and his colleagues, examining messenger RNA molecules, which are copies of genes that cells use for their functioning. The analysis revealed that these cells are organized into nine distinct clusters. Some of these clusters stimulate appetite, while others suppress it, and they adjust their production of messenger RNAs based on whether the mice are fed or fasting.

“We now have a much better understanding of the variety of cell types and the physiological processes that promote feeding in the central amygdala,” states Rüdiger Klein.

“Our research unveils, for the first time, that the ‘hunger hormone’ ghrelin also exerts its effects on cells in the central amygdala.”

In that region, it activates a small subset of cell clusters, collectively characterized by the presence of the protein Htr2a, to enhance feeding.

It was found by the scientists that the activity of Htr2a neurons was triggered after an overnight fast or when stimulated by the hormone ghrelin. The presentation of food to the mice also elicited a response from these cells.

Ghrelin the multitasker

Multiple functions are believed to be performed by ghrelin, as explained by Christian Peters.

“When mice are hungry, the activation of appetitive brain regions by ghrelin predisposes the animals to eat. Additionally, the hormone increases activity in brain circuits, such as the amygdala, which confer rewards and likely serve as an incentive to consume more food.”

Thus, ghrelin enhances the palatability of food based on the satiety level of the mice.

During a fasting diet, when the animals experienced intense hunger, the activity of Htr2a neurons was not necessary to initiate feeding, presumably due to the diminished importance of food tastiness under such conditions.

“Other brain circuits, such as the hypothalamus, which regulate the body’s metabolism, take over and signal the mice about the importance of eating for survival,” states Christian Peters.

Feeling hungry or satiated profoundly affects physical and emotional well-being, as most people are aware of the pleasures associated with eating delicious food.

“The neuronal networks that convey these feelings are evidently interconnected with those that control eating, although the exact nature of their mutual influence is not fully understood,” says Rüdiger Klein.

“If we unravel these connections, we will gain a better understanding of the neuronal processes involved in pathological eating behaviors, including overeating,” concludes Christian Peters.

“There are numerous biological factors contributing to such complex behavior, and we need to examine the physiological processes to comprehend these factors.”

Ultimately, this knowledge could potentially lead to innovative therapeutic approaches for mitigating eating disorders.

Currently, the research establishes the foundation for further investigations into the involvement of specific neuron populations in the neuronal circuits that regulate feeding. It also adds another significant piece to the puzzle of comprehending how the brain coordinates behavior.



Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding

The central amygdala (CeA) consists of numerous genetically defined inhibitory neurons that control defensive and appetitive behaviors including feeding. Transcriptomic signatures of cell types and their links to function remain poorly understood.

Using single-nucleus RNA sequencing, we describe nine CeA cell clusters, of which four are mostly associated with appetitive and two with aversive behaviors.

To analyze the activation mechanism of appetitive CeA neurons, we characterized serotonin receptor 2a (Htr2a)–expressing neurons (CeAHtr2a) that comprise three appetitive clusters and were previously shown to promote feeding. In vivo calcium imaging revealed that CeAHtr2a neurons are activated by fasting, the hormone ghrelin, and the presence of food.

Moreover, these neurons are required for the orexigenic effects of ghrelin. Appetitive CeA neurons responsive to fasting and ghrelin project to the parabrachial nucleus (PBN) causing inhibition of target PBN neurons.

These results illustrate how the transcriptomic diversification of CeA neurons relates to fasting and hormone-regulated feeding behavior.

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding” by Rüdiger Klein et al. Science Advances