Most of us think of memory as strictly a brain function, formed and stored within the skull. In rats, however, the gut also plays a role—at least when it comes to memories of food.
A team of researchers from the University of Southern California studied how signals from the stomach and intestines reach the brain during eating. The study’s findings were published in the journal Nature Communications.
These signals travel along the vagus nerve, the primary nerve connecting the gut to the brain. As the rats ate, cells released increased amounts of a chemical called acetylcholine into the hippocampus—the part of the brain responsible for forming new memories. The team monitored this process in real time using a light-based sensor implanted in the brain.
Acetylcholine levels in the hippocampus rose within seconds of the rat starting to eat and dropped shortly after the animal stopped. The signal intensified as the meal progressed, peaking during the final bites. After the rat finished eating, the elevated levels persisted for several minutes rather than dropping immediately.
To determine exactly what triggered this response, the team compared several different liquids. Both sugar water and a corn oil-based solution raised acetylcholine levels in the hippocampus.
A calorie-free sweetener called saccharin had no effect, even though the rats found it just as palatable. They consumed more of the saccharin solution, suggesting the difference reflected the presence of nutrients rather than taste or volume.
Cholecystokinin, a gut hormone that signals satiety via the vagus nerve, triggered a similar acetylcholine response. Amylin, a satiety hormone that acts independently of the vagus nerve, did not trigger this response.
“We believe this mechanism likely evolved to help animals remember important information about food sources,” said study co-author Logan Lauer.
To determine whether the nerve itself played a role, the team severed the vagus nerve in some rats. Without it, the response to food intake triggered by acetylcholine disappeared. In another group, scientists destroyed specific brain cells that release acetylcholine into the hippocampus. This also eliminated the response.
Severing the nerve also reduced the level of a protein that helps the brain package acetylcholine for release. Levels of two other acetylcholine-related proteins remained unchanged.
The team then conducted direct memory tests. Hungry rats explored a circular table (approximately 122 cm in diameter) featuring 18 holes; one hole contained a tunnel leading to food. In subsequent trials, healthy rats returned to the correct location. Rats with severed vagus nerves or depleted acetylcholine-producing cells performed no better than chance.
The location of the food changed daily, requiring the rats to memorize a new spot each time. This turned the trial into a test of rapid, immediate memory rather than a test of ingrained habit. During the experiment, acetylcholine levels in healthy rats rose when they identified the correct hole. This increase was absent in rats with severed vagus nerves.
The timing of feeding also played a role. Some rats were fed an unhealthy diet—similar to cafeteria food, including chips, candy, and sugary drinks—for 30 days before returning to their normal diet. These rats no longer exhibited a sustained rise in acetylcholine levels after eating. They also performed worse on a test requiring them to remember the location of food, though not as poorly as rats lacking the relevant nerve or brain cells.
Advertisement
granelle.ru
Their satiety signals were also blunted. A dose of cholecystokinin—which suppresses appetite in normal rats—had virtually no effect on these animals. Over a six-day period, the rats fed the unhealthy diet consumed more than the others. This excess intake was driven primarily by larger portion sizes rather than more frequent meals.
The study was conducted on male rats, and a similar system has not yet been demonstrated in humans. The pathway described by the team—running from the gut to the brainstem and on to the memory center—remains a working model rather than a definitively mapped circuit.
Unlike rats lacking the specific nerve endings or cells, the rats fed the unhealthy diet still managed to remember information better than chance would predict. Researchers hypothesize that other signals from the brain may partially compensate for the weakened signal coming from the gut.
They point to a second gut hormone, released later in the digestive process, which may help maintain elevated acetylcholine levels after a meal has ended. This aspect of the model has not yet been tested.
Signs of the same connection were also found in humans. Patients in Taiwan who underwent a partial vagotomy (severing of part of the vagus nerve) to treat ulcers subsequently developed dementia at higher rates than comparable patients, although this finding could not prove that the surgery itself was the cause.
“Disrupted acetylcholine signaling in the hippocampus is one of the earliest neurochemical changes in Alzheimer’s disease,” said Professor Scott Kanoski of the University of Southern California. “By identifying that this system is enhanced by vagus nerve signals originating in the gut, we can develop new therapeutic targets, using this information to explore approaches that act on the vagus nerve, such as vagus nerve stimulation.”
About the Author
