Food is a kind of reward, and the better it tastes, the more rewarding it feels. New research in mice identifies the neurons and brain circuits that regulate how much pleasure the rodents take in eating. Some of these neuronal mechanisms are also involved in reward processing.

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New research identifies appetite-controlling brain cells in mice that are likely to exist in humans, too. The findings may have significant implications for people with eating disorders.

A new study published in the journal Nature Neuroscience finds neurons and neuronal circuits that control how much pleasure mice – and probably humans, too – get from eating.

Researchers at the Max Planck Institute of Neurobiology in Martinsried, Germany – in collaboration with those at the Friedrich Miescher Institute in Basel, Switzerland – set out to examine the brain mechanisms that govern appetite and food consumption.

The first three authors of the study are Amelia Douglass, Hakan Kucukdereli, and Marion Ponserre – all three doctoral students who, on this study, worked together with other researchers and senior author Prof. Rüdiger Klein, director at the Max Planck Institute of Neurobiology.

As the authors explain, it is known that our reward-seeking and reward-processing brain processes also control appetite, but how or whether other brain areas may also play a role is not entirely known.

The team also explains that previous research has shown that a brain region known as the central nucleus of the amygdala (CeA) is involved in feeding and reward processing, but precisely what neurons and circuits drive these behaviors has not been clear.

The amygdala is the brain region that is key for processing emotions, making decisions, responding to emotionally demanding situations, and learning by association with frightening or pleasurable events.

As Prof. Klein explains, researchers from the California Institute of Technology in Pasadena already pointed out that a class of neurons called PKC-delta neurons, which reside in this CeA area, can make mice stop eating.

“I found this study on ‘anorexia neurons’ in the amygdala fascinating,” says Prof. Klein. So, for the new research, the scientists set out to identify whether or not there were other neurons implicated in appetite and food consumption.

The team focused on a different population of CeA-based neurons called HTR2a neurons.

The researchers used a series of innovative optogenetic and pharmacogenetic techniques in order to examine these neurons. Optogenetics is a cutting-edge technique that genetically alters neurons in order to make them sensitive to light. Then, with the right frequency of light, the researchers are able to selectively switch on and off certain neurons.

Similarly, the pharmacogenetic tool called deep-brain calcium imaging allowed the researchers to genetically alter neurons so that they became fluorescent, and therefore traceable, upon contact with calcium.

Another technique used for tracing neurons relied on using the rabies virus. Viral neuronal tracing techniques have been revolutionizing neuroanatomy in recent years, allowing neuroscientists to map the connections in the brain.

Using these techniques, the researchers were able to show – in vivo – that HTR2a neurons “modulate food consumption, promote positive reinforcement, and are active during eating.”

“Basically we showed that HTR2a cells have a positive effect on food consumption in mice, and that the mice like it when these cells are active,” says Douglass.

Specifically, the team showed that switching on these neurons made the mice eat for longer. In fact, this effect was all the more evident when the mice were already full.

Additionally, further experiments showed that the mice enjoyed having these neurons activated; using a contraption devised for the study, the rodents could turn on these neurons by pressing a switch with their snout.

Co-lead author Kucukdereli details the findings, saying, “It was clear that the mice liked having active HTR2a cells – they could not leave the switch alone.”

“When we specifically ablated only the HTR2a cells, the mice continued to eat regularly and did not lose weight in the long-term, and when we inactivated the cells the mice did not eat as much of appetizing food even if they were hungry.”

Importantly, these neurons seemed to exert this influence on the mice’s appetite only once the rodents had already started to eat. The HTR2a cells did not appear to be active when the mice were simply made aware that they were about to receive food.

This suggested to the researchers that HTR2a may impact how food tastes. In fact, the researchers were able to “make” the mice enjoy a certain taste that they had not previously preferred simply by switching on these cells.

Finally, the research highlights an intriguing dynamic between the HTR2a neurons and PKC-delta ones that previous research had identified in the amygdala. After tracing the neuronal networks, the researchers revealed a synaptic circuit that suggests HTR2a neurons and PKC-delta neurons can mutually inhibit each other.

“Eating something bad activates PKC-delta cells, thus inhibiting the HTR2a cells, causing the animals to stop,” explains co-lead author Ponserre. “By contrast, eating something delicious activates HTR2a cells, thus inhibiting PKC-delta cells, causing food consumption to be linked to reward.”

Certainly we have a good starting point for investigating the links between food consumption, emotional state and the reward system. There are likely to be similar cells and circuits in the human brain, and this could also be an interesting area of research for helping people with eating disorders.”

Prof. Rüdiger Klein