Ghrelin Impacts Ventral Hippocampus to Drive Behavior

not hungry child

According to a new study by University College London researchers, ghrelin – a hunger hormone produced in the gut – can directly impact a decision-making part of the brain in order to drive an animal’s behavior. The study in mice is the first to show how hunger hormones can directly impact activity of the brain’s hippocampus when an animal is considering food.

“We all know our decisions can be deeply influenced by our hunger, as food has a different meaning depending on whether we are hungry or full. Just think of how much you might buy when grocery shopping on an empty stomach. But what may seem like a simple concept is actually very complicated in reality; it requires the ability to use what’s called ‘contextual learning,”

Lead author Dr. Andrew MacAskill said.

The researchers discovered that a part of the brain important for decision-making is surprisingly sensitive to hunger hormone levels produced in our gut, which they believe helps our brains contextualize our eating choices.

Motivational State Affects Processing

The researchers placed mice in an arena with food and observed how the mice acted whether hungry or full, while imaging their brains in real time to explore neuronal activity. The mice all spent time inspecting the food, but only the hungry ones started eating.

The researchers were focusing on brain activity in the ventral hippocampus (the underside of the hippocampus), a decision-making part of the brain which is understood to help us form and use memories to guide our behavior.

When animals approached food, activity in a subset of brain cells in the ventral hippocampus increased, and this activity inhibited the animal from eating.

However, when the mouse was hungry, there was less neuronal activity in this location, and the hippocampus no longer prevented the animal from eating. The researchers found that this corresponded to high levels of the hunger hormone ghrelin in the blood.

Ghrelin Receptor Removal

To add to these findings, the UCL researchers were able to experimentally make mice act as if they were full by activating these ventral hippocampus neurons, causing them to stop eating even when they were hungry. The scientists accomplished this outcome once more by deleting the ghrelin receptors from these neurons.

Prior studies have shown that the hippocampus of animals, including non-human primates, has receptors for ghrelin, but there was scant evidence for how these receptors work.

These results demonstrate how ghrelin receptors in the brain are used, showing that the hunger hormone can cross the blood-brain barrier (which prevents many substances in the blood from reaching the brain) and directly impact the brain to drive activity, controlling a circuit in the brain that is likely to be the same or similar in humans.

Next Steps

The scientists are expanding their research to investigate if hunger affects learning or memory by having mice execute non-food-specific activities differently depending on how hungry they are. They believe that more research will shed light on whether similar processes exist for stress or thirst.

“It appears that the hippocampus puts the brakes on an animal’s instinct to eat when it encounters food, to ensure that the animal does not overeat; but if the animal is indeed hungry, hormones will direct the brain to switch off the brakes, so the animal goes ahead and begins eating,”

Dr. MacAskill said.

The researchers hope their findings could contribute to research into the mechanisms of eating disorders to see if ghrelin receptors in the hippocampus might be implicated, as well as with other links between diet and other health outcomes such as risk of mental illnesses.

“Being able to make decisions based on how hungry we are is very important. If this goes wrong it can lead to serious health problems. We hope that by improving our understanding of how this works in the brain, we might be able to aid in the prevention and treatment of eating disorders,”

first author Dr. Ryan Wee said.

  1. Ryan Wee et al. Internal state dependent control of feeding behaviour via hippocampal ghrelin signalling. Neuron (2023). DOI: 10.1016/j.neuron.2023.10.016