Journal Club

Highlighting recent, timely papers selected by Academy member labs

Journal Club: Food first—Safety, friends, and water can come later

What basic drive dominates? Hunger wins out for mice. Credit: Wikimedia/Tiia Monto CC BY SA 3.0

What basic drive dominates? Hunger wins out for mice. Credit: Wikimedia/Tiia Monto CC BY SA 3.0

Suppose you’re hungry, but also cold. Your dog is barking at someone at the door, and you see your spouse heading toward the fridge—you wonder if he will take the last of the leftover pizza. With many competing factors vying for attention, what’s a brain to do?

Michael Krashes, a neuroscientist at the National Institute of Health in Bethesda Maryland, and his colleagues examined how very hungry mice respond when they must choose between eating and avoiding the smell of a predator, drinking water when thirsty, or interacting with other mice. They wanted to investigate how hunger can influence these competing drive states.

Food, they found, gets the priority, according to research published in Neuron on October 5. And a special group of neurons seems to be responsible. The researchers used three groups of mice. Two groups expressed a fluorescent protein (GFP) in their Agouti-related peptide (AgRP) neurons. One group was fed as much food as they wanted; the other group fasted for 24 hours. The third set was treated with a light-responsive protein, allowing the researchers to activate AgRP neurons.

In previous work, the team had shown these neurons are absolutely needed for regulating body weight. If they’re disrupted animals can starve to death, if the neurons are overactive the animals become obese.

The researchers found that activated AgRP neurons caused the third group of mice to mimic the behaviors of naturally hungry mice, while non hungry mice (that had access to all the food they wanted) acted appropriately to behavioral cues—interacting socially or responding with fear to the scent of a predator.

“I think the take home points [from the current study] are that AgRP neurons signal to the animal to find caloric substrates even at the costs of other important needs such as thirst, avoiding predation, defending territory, or mating,” says Krashes.

He notes that our brains evolved over a long period of time, when finding food was a more task than it is today. “We had to contend with a number of variables taken for granted in most of the world at present. We had to deal with harsh climate conditions, predation, defending our territory from rivals and other competing drives like thirst and the opportunity to mate and pass down our DNA,” he says. “Of course, all of these needs are incredibly important and since we can only perform one action at a time, a hierarchy starts to emerge.”

Zachary Knight, a neurologist at University of California, San Francisco, who was not involved in the work, says the paper is illuminating in the context of other work that shows stimulating other neurons (LH-Vgat neurons) promotes feeding, but doesn’t suppress competing drives.

“While it makes intuitive sense that different types of neurons would control different aspects of feeding behavior, until recently this has been difficult to demonstrate because the tools and knowledge base necessary to manipulate discrete circuit elements has not existed,” Knight says.

For Krashes, the most interesting aspect of the work is that simulating a few thousand hypothalamic neurons (AgRP neurons) will shift the innate behavior of an animal. “These neurons truly encode hunger and tell the animal to find food regardless of other contending drives,” he says, adding that humans have these exact same neurons.

One of the problems of modern life, Krashes says, is that our brains have a problem adapting to the smorgasbord of calorie-dense options so readily available around us, “I can certainly imagine a future,” he adds, “where drugs are targeted to interact and impact [those neurons] to modulate feeding.”

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