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Researchers find how hunger hormones impact decision-making brain area to drive behaviour

ANI Nov 17, 2023

A hunger hormone generated in the gut can directly influence a decision-making area of the brain, according to a recent study by UCL (University College London) researchers.

The study in an experimental model, published in Neuron, is the first to illustrate how hunger hormones can directly influence hippocampal activity when an experimental model is thinking about 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," stated lead author Dr Andrew MacAskill (UCL Neuroscience, Physiology, and Pharmacology). Consider how much you may spend if you go food shopping on an empty stomach. However, what appears to be a simple concept is actually quite complex.

"We found that a part of the brain that is crucial for decision-making is surprisingly sensitive to the levels of hunger hormones produced in our gut, which we believe is helping our brains to contextualise our eating choices."

For the study, the researchers put the experimental model in an arena that had some food and looked at how the experimental model acted when they were hungry or full while imaging their brains in real time to investigate neural activity. All of the experimental models spent time investigating the food, but only the hungry experimental models would then begin eating.

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

The scientists found that activity in a subset of brain cells in the ventral hippocampus increased when experimental models approached food, and this activity inhibited the experimental models from eating.

However if the experimental model was hungry, there was less neural activity in this area, so the hippocampus no longer stopped the experimental model from eating. The researchers found this corresponded to high levels of the hunger hormone ghrelin circulating in the blood.

Adding further clarity, the UCL researchers were able to experimentally make experimental models behave as if they were full, by activating these ventral hippocampal neurons, leading experimental models to stop eating even if they were hungry. The scientists achieved this result again by removing the receptors for the hunger hormone ghrelin from these neurons.

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

This finding has demonstrated how ghrelin receptors in the brain are put to use, showing the hunger hormone can cross the blood-brain barrier (which strictly restricts 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.

Dr MacAskill added: "It appears that the hippocampus puts the brakes on an experimental model instinct to eat when it encounters food, to ensure that the experimental model does not overeat - but if the experimental model is indeed hungry, hormones will direct the brain to switch off the brakes, so the experimental model goes ahead and begins eating."

The scientists are continuing their research by investigating whether hunger can impact learning or memory, by seeing if experimental models perform non-food-specific tasks differently depending on how hungry they are. They say additional research might also shed light on whether there are similar mechanisms at play for stress or thirst.

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.

First author Dr Ryan Wee (UCL Neuroscience, Physiology & Pharmacology) said: "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." 

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