Neuroscience study identifies role of melanin-concentrating hormone neurons in non-hunger-driven eating

Researchers have uncovered new insights into how a specific group of brain cells, melanin-concentrating hormone neurons, influence food-related behaviors. Published in the Journal of Neuroscience, the study demonstrated that these neurons enhance the rewarding value of food consumption. Interestingly, their activation does not cause animals to eat more food overall, suggesting a separation between the mechanisms driving food reward and those driving food consumption.

Melanin-concentrating hormone (MCH) neurons are a specialized group of brain cells located in regions such as the lateral hypothalamus and zona incerta. As their name suggests, these neurons produce the neuropeptide called melanin-concentrating hormone—a chemical messenger that helps regulate behaviors like eating, sleeping, and experiencing pleasure or reward. What makes MCH neurons particularly intriguing is that they send signals to many different parts of the brain.

Previous research has shown that altering the activity of these neurons can affect energy balance, with studies linking their activation to increased food consumption and weight gain in rodents. However, their exact role in non-hunger-driven, or non-homeostatic, feeding behaviors—such as eating for pleasure—remains unclear.

“I’ve always been interested in the reasons people (or animals) choose to do what they do, whether that be working, relaxing, eating, sleeping, etc,” said Katherine Furman, a PhD student at the Michigan Neuroscience Institute at the University of Michigan.

“When I learned of MCH neurons, which seem to have involvement in a lot of those behaviors, I was very interested in how this neuron population is able to have all of those roles. With this research, we’ve been able to take a set of neurons which seems to have many different functions, and narrow down a pretty specific role for just one subpopulation of those neurons. Getting at the ‘why do we do what we do’ question in this way has been very exciting for me.”

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To investigate how MCH neurons contribute to food-related behaviors, the researchers focused on understanding their role in the nucleus accumbens, a brain region heavily involved in processing reward. To achieve this, they used genetically modified mice that allowed for precise control of MCH neurons. They employed optogenetics, a technique that uses light to activate or inhibit specific neurons, enabling them to directly study the effects of these neurons on behavior.

The study involved two key experimental setups. In the first, the researchers observed how optogenetic activation of MCH neurons affected food consumption in a controlled environment. Mice were housed in cages equipped with automated feeders that tracked how much food they consumed during periods of light-based activation.

The second setup involved an optogenetics-reinforced consumption assay, which gave mice the opportunity to choose between different combinations of food and neuron activation. For example, the mice could nose-poke to access a food pellet, optogenetic stimulation of the neurons, or a combination of both. This allowed the researchers to assess not just how much the mice ate but also how much they valued the reward associated with food.

The researchers found that optogenetic activation of MCH neurons in the nucleus accumbens did not lead to an increase in overall food consumption, challenging previous assumptions that these neurons directly drive feeding. Instead, the activation made food more rewarding when paired with stimulation, as the mice consistently chose ports that provided both food and neuron activation. This suggests that MCH neurons in the nucleus accumbens enhance the perceived value of food without necessarily promoting eating.

“I was surprised that we didn’t see an increase in feeding across our optogenetic activation experiments,” explained Christian Burgess, an assistant professor at the University of Michigan and senior author of the study. “Much of the early work investigating the function of MCH peptide, and the neurons that release it, suggested that they had a strong role in promoting food intake.”

“A few more recent studies using newer tools, like optogenetics and chemogenetics, activated the whole population of MCH neurons and showed no increases in food intake, or even a decrease. My initial hypothesis was that the nucleus accumbens projection MCH neurons would drive strong baseline food intake, but that did not end up being the case.”

Interestingly, the researchers also found that stimulating these neurons had no impact on rapid eye movement (REM) sleep, even though MCH neurons in other brain regions are known to increase this type of sleep. This highlights the idea that different projections of MCH neurons serve distinct functions, depending on where in the brain they are activated. For example, neurons projecting to the nucleus accumbens specifically influenced reward-related behaviors without affecting sleep or basic feeding drives.

“This is important because it separates the behavioral role of those nucleus accumbens-projecting MCH neurons from the MCH neurons projecting elsewhere, which don’t serve the same role,” Furman told PsyPost. “Isolating a set of neurons that can attribute reward value to food has interesting implications for patients struggling with eating disorders or obesity. If pharmaceutical developers are able to use these findings to develop clinical treatments that help people regulate their food intake, this could help lead to better treatments.”

The study also uncovered differences in how male and female mice responded to the activation of MCH neurons. In particular, male mice exhibited more pronounced effects from MCH neuron activation compared to females.

“When looking at animals’ choices of which foods to eat, I was surprised when we analyzed the data separately for male and female mice: it appears as though there might be a different relationship between nucleus accumbens-projecting MCH neurons and food intake, based on the sex of the animal,” Furman explained. “This isn’t something we fully understand yet, and the next set of experiments I’m going to do are planning to investigate that a little bit more.”

While the study provides important insights, it also has limitations. “Optogenetics, the experimental technique we use to artificially activate MCH neurons in this study, is just that – an artificial type of activation,” Furman noted. “This technique is very useful experimentally, in order to see what happens when we strongly activate (or inhibit) a genetically defined population of neurons. But it may not do a good job of replicating what the natural activity pattern of these cells looks like.”

“It may be more like using a jackhammer to accomplish a task that really only needs a small twist from a screwdriver. So while this work certainly informs our understanding of what MCH neurons can do, it may not be a good representation of what they do do.”

One promising avenue for future research is exploring how MCH neurons interact with other brain regions and neurotransmitter systems. Although this study focused on their role in the nucleus accumbens, MCH neurons project widely throughout the brain, suggesting they may influence multiple systems.

“MCH neurons project broadly throughout the brain and have been implicated in many important behaviors, including feeding, sleep, reward, learning, and anxiety,” Burgess explained. “These neurons also release a number of neurotransmitters aside from MCH peptide. We aim to identify how MCH neurons regulate these disparate behaviors: through which efferent projections? Release of which transmitters? Which postsynaptic neurons? Using modern systems neuroscience approaches and creative behavioral paradigms we hope to be able to answer these questions in the lab.”

This line of research could lead to more effective treatments for disorders involving non-homeostatic feeding, such as obesity and eating disorders.

“My personal involvement with this work will come to an end when I graduate and defend my PhD dissertation,” Furman said. “So although I won’t be personally involved for much longer, I’d love to see this work lead to a better understanding of how the brain decides when to eat, and which foods we choose to engage with. We already know that there’s reasons to eat other than hunger; things like taste, desire, availability, and cravings. It’s this non-hunger-related type of eating that seems dysregulated in patients with eating disorders or obesity. So developing a better field-wide understanding of that phenomenon will be crucial in the coming years.”

“I will be graduating and defending my PhD this summer!” she added. “If anyone reading this is looking for a new hire in science writing and communication, with an expertise in neuroscience, they should reach out to me.”

The study, “Melanin concentrating hormone projections to the nucleus accumbens enhance the reward value of food consumption and do not induce feeding or REM sleep,” was authored by Katherine L. Furman, Lorelei Baron, Hannah C. Lyons, Timothy Cha, Jack R. Evans, Jayeeta Manna, Limei Zhu, Joanna Mattis, and Christian R. Burgess.