Hunger for Knowledge: Appetite hormone may stimulate memory

A hormone that’s been tied to hunger may also play a pivotal role in creating and retrieving memories, according to a study in mice. These findings could spur new strategies for improving learning and memory in people.

When the stomach is empty, its lining cells secrete a hormone called ghrelin. Previous studies have shown that ghrelin migrates through the bloodstream and into the brain, where it stimulates receptors on nerve cells in the hypothalamus. This structure, found at the base of the brain, subsequently triggers appetite.

Researchers have also found ghrelin receptors scattered throughout the brain beyond the hypothalamus. “The question was, ‘What is ghrelin doing in the rest of the brain, if anything?'” says Tamas Horvath, a neuroscientist at Yale University School of Medicine.

Horvath and his team focused their attention on ghrelin’s role in the hippocampus, a brain area involved in learning and memory and that’s littered with ghrelin receptors. The scientists started by injecting some normal mice with extra ghrelin and others with an equal amount of saline over the course of several days. When they examined the animals’ brains, they found that hippocampal cells in those mice that had received ghrelin had about a quarter more dendritic spines, which are specialized nerve cell connections associated with learning.

The scientists found a similar scenario when they compared normal mice with mice genetically altered so that they didn’t make any ghrelin. The ghrelin-deficient animals had about 25 percent fewer dendritic spines than normal mice did.

To see whether these anatomical differences could affect learning and memory, Horvath’s team compared ghrelin and saline-injected mice in a variety of memory-retention tasks, such as recalling where treats were hidden in a maze or remembering sections in another maze that delivered a mild shock to the animals’ feet. Mice treated with ghrelin learned these locations significantly faster than the saline-treated animals did.

The researchers compared how normal mice and mice lacking the gene to make ghrelin reacted when an old toy in their cages was swapped for a new one. Normal mice spent several extra minutes investigating the new toy, which researchers take as an indication that an animal remembers a missing object. However, the ghrelin-deficient mice didn’t spend any more time with the new toy than with other toys in their cages. When the researchers injected these mice with ghrelin, they investigated new toys as much as normal mice did.

The researchers report their findings in the March Nature Neuroscience.

The results make sense in the context of evolution, says Mark Mattson, a neuroscientist at the National Institute on Aging’s Intramural Research Program in Baltimore. Previous studies by his lab and others have shown that hunger increases an animal’s brain activity. “It makes sense that hungry animals need to enhance their learning and memory so, for example, they can remember where a food source is and return to it,” he says.


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